Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Boscia F; Elkjaer ML; Illes Z; Kukley M

doi:10.3389/fncel.2021.685703

Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Affiliations

1. Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University of Naples "Federico II", Naples, Italy.
Authors
Boscia F¹
(1 author)
2. Neurology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Authors
Elkjaer ML²
Illes Z²
(2 authors)
3. Achucarro Basque Center for Neuroscience, Leioa, Spain.
Authors
Kukley M³
(1 author)

ORCIDs linked to this article

Frontiers in Cellular Neuroscience, 25 Jun 2021, 15:685703
https://doi.org/10.3389/fncel.2021.685703 PMID: 34276310 PMCID: PMC8282214

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Abstract

Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K⁺, Ca²⁺, Na⁺, and Cl^- channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na⁺ channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na⁺ homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K⁺ channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl^- channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability.

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Front Cell Neurosci. 2021; 15: 685703.

Published online 2021 Jun 25. https://doi.org/10.3389/fncel.2021.685703

PMCID: PMC8282214

PMID: 34276310

Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Francesca Boscia,^1,^* Maria Louise Elkjaer,^2,³ Zsolt Illes,^2,^3,⁴ and Maria Kukley^5,^6,^*

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Abstract

Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K⁺, Ca²⁺, Na⁺, and Cl⁻ channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na⁺ channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na⁺ homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K⁺ channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl⁻ channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability.

Keywords: multiple sclerosis, progressive, white matter, lesions, ion channels, transcriptome

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Introduction

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) affecting more than 2 million people worldwide. MS lesions in CNS white matter (WM) are multiple focal areas of myelin loss accompanied by inflammation, gliosis, phagocytic activity, and axonal damage (Compston and Coles, 2008; Kuhlmann et al., 2017; Filippi et al., 2018; Rommer et al., 2019). Available MS therapies have little benefit for secondary-progressive MS (SPMS) patients, who develop progressive disability after a disease course characterized by inflammatory attacks. Therefore, promoting neuroprotection and remyelination are important therapeutic goals to prevent irreversible neurological deficits and permanent disability.

Ion channels play a fundamental role in maintaining WM integrity and regulating function of axons, interstitial neurons (Sedmak and Judas, 2021), glia, and vascular cells. Dysregulation of ionic homeostasis in the WM during demyelination is decisive for axonal damage and cell death and may interfere with tissue repair processes (Boscia et al., 2020). Furthermore, MS may involve an acquired channelopathy (Waxman, 2001; Schattling et al., 2014). Hence, selectively targeting ion channels in WM represents an attractive strategy to overcome axonal and glial impairment and prevent disease progression.

Recently, transcriptomic studies have considerably increased our insight into gene expression changes occurring in the MS brain (Elkjaer et al., 2019; Jakel et al., 2019; Schirmer et al., 2019). Aiming at identifying the ion channel genes governing WM dysfunction in SPMS brain, we analyzed the recent bulk RNA-sequencing (RNA-seq) datasets by using the MS-Atlas (Elkjaer et al., 2019; Frisch et al., 2020). We put a special emphasis on the distribution of shared and unique genes encoding ion channels in chronic active (CA), active (AL), inactive (IL), and remyelinating (RL) lesions, and normal-appearing white matter (NAWM) compared to control WM (Figures 1A,B, Table 1). We identified uniquely expressed ion channel genes: 34 genes in CA, 9 in IL, 1 in AL, as well as 2 genes in all lesions and NAWM (Figures 1, ,2,2, Table 1). The CA lesions displayed the highest number of upregulated ion channels genes while downregulated ion channels genes were more consistently found in ILs (Figure 1C). Next, we explored recent single-nuclei RNA-seq (snRNA-seq) datasets to identify the expression of dysregulated ion channel genes in cell clusters in the WM of control and SPMS brain (Jakel et al., 2019; Tables 1, ,2,2, Figure 3).

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Figure 1

The transcriptional landscape of ion channels in different types of white matter brain lesions from patients with secondary progressive multiple sclerosis. (A) The percentage of significantly differentially expressed genes coding for ion channels among all dysregulated genes and within each lesion type [chronic active (CA), active (AL), inactive (IL), and remyelinating (RL)] and normal-appearing white matter (NAWM) compared to control white matter are indicated. (B) The Venn diagram shows the number of lesion-specific differentially expressed genes coding for ion channels and the number of overlapping genes among the lesion types. (C) The number of significantly differentially upregulated (red) and downregulated (blue) genes in each type of while matter lesion and NAWM compared to control white matter are indicated.

Table 1

Expression and distribution of unique and overlapping genes coding for ion channels within SPMS lesions.

Protein	Gene	Bulk lesion^a	Fold change Up (+)/down (–) regulated (compared to control WM)^a	Current type/conductance	Highly expressed in WM clusters of human brain^b
K⁺ channels
K_v 1.1	KCNA1	CA	+1.42	Delayed rectifier
K_v 1.2	KCNA2	CA	+1.06	Delayed rectifier	neuron2
K_v 1.3	KCNA3	AL, CA, IL	+1.67 (AL); +1.35 (CA); +1.34 (IL)	Delayed rectifier
K_v 1.4	KCNA4	CA	+1.34	A-type
K_v 1.5	KCNA5	AL, RL	+0.86 (AL); +1.36 (RL)	Delayed rectifier
K_v 2.2	KCNB2	CA	+1.56	Delayed rectifier	Neuron1, 2, 3, 4, 5
K_v 2.1	KCNB1	CA	+1.26	Delayed rectifier	Neuron1, 2, 3
K_v 3.3	KCNC3	CA	+0.87	A-type
K_v 3.4	KCNC4	AL, IL	+0.81 (AL); +0.72 (IL)	A-type
K_v 4.2	KCND2	CA	+0.95	A-type	OPC, COP, neuron1,3
K_v 4.3	KCND3	AL, CA, IL	+0.63 (AL); +0.86 (CA); +0.93 (IL)	A-type	neuron1, 2, 3
K_v 6.1	KCNG1	AL, RL	+2.72 (AL); +3.7 (RL)	Modifier of Kv 2
K_v 7.1	KCNQ1	AL, CA	+0.91 (AL); +0.75 (CA)	M-type
K_v 7.2	KCNQ2	CA	+0.75	M-type	neuron1, 2
K_v 7.3	KCNQ3	CA	+0.85	M-type	ImOLGs, neuron1, 2, 3, 5, microglia/macrophages
K_v 7.4	KCNQ4	AL, CA, IL, RL	+1.19 (AL);+ 0.92 (CA); +1.36 (IL); +2.22 (RL)	M-type
K_v 7.5	KCNQ5	CA	+1.69	M-type	Neuron1, 2, 3, 5
K_v 8.1	KCNV1	CA	+1.48	Modifier of Kv 2
K_v 9.2	KCNS2	CA	+0.90	Modifier of Kv 2
K_v 9.3	KCNS3	AL, IL, RL, NAWM	−2.72 (AL); −1.5 (IL); −1.98 (RL); −0.71 (NAWM)	Modifier of Kv 2
K_v 10.1/EAG1	KCNH1	CA, IL	+0.81 (CA); +0.93 (IL)	Delayed rectifier	Neuron1, 2, 3
K_v 10. 2/EAG2	KCNH5	CA	+1.38	Delayed rectifier	Neuron2
K_v 11.3/ERG3	KCNH7	CA	+1.38	Delayed rectifier	Neuron1, 2, 3, 5
K_v 12.1/ELK1	KCNH8	AL, CA, IL, RL, NAWM	−1.25 (AL); −1.4(CA); −2.05 (IL); −2.38 (RL); −0.62 (NAWM)	Delayed rectifier	Oligo3, Oligo4, Oligo6
TREK1	KCNK2	CA	+1.03	Leak, two pore
TWIK2	KCNK6	AL, IL	+1.57 (AL); +0.82 (IL)	Leak, two pore
TREK2	KCNK10	AL	−0.65	Leak, two pore
K_Ca1.1	KCNMA1	AL, CA, IL	+0.69 (AL); +0.87 (CA); +0.7 (IL)	Calcium-Activated	OPC, neuron1, 2, 3, 5, microglia/macrophages
K_Ca2.3	KCNN3	IL	−0.7	Calcium-Activated	Astrocytes1
K_Na1.1	KCNT1	CA	+1.24	Sodium-Activated
K_Na1.2	KCNT2	CA, IL	+0.92 (CA); +1.15 (IL)	Sodium-Activated	Neuron1, 2, 3, pericytes, vascular smooth cells
K_ir2.1	KCNJ2	AL, CA, IL, RL	−0.54 (AL); −0.48 (CA); −0.54 (IL); −0.92 (RL)	Inward rectifier
K_ir3.4	KCNJ5	AL, CA, RL, NAWM	+2.58 (AL); +1.56 (CA); +1.9 (RL); +1.53 (NAWM)	Inward rectifier
K_ir3.2	KCNJ6	CA	+1.34	Inward rectifier	Neuron1, 2, 3
K_ir6.1	KCNJ8	AL, IL	+0.74 (AL); +0.71 (IL)	Inward rectifier
K_ir3.3	KCNJ9	CA, RL	−0.52 (CA); −0.9 (RL)	Inward rectifier
K_ir4.1	KCNJ10	IL, RL	−1.06 (IL); −1.09 (RL)	Inward rectifier	Oligo5
K_ir5.1	KCNJ16	CA	+1.27	Inward rectifier
Na⁺ channels
Na_v1.1	SCN1A	CA	+1.12	TTX-sensitive	OPC, COP, neuron1, 2, 3, 4, 5
Na_v1.2	SCN2A	CA	+1.1	TTX-sensitive	Neuron1, 2, 3, 4, 5
Na_v1.3	SCN3A	CA	+0.87	TTX-sensitive	OPC, neuron1, 2, 3, 5
Na_v1.6	SCN8A	CA	+1.15	TTX-sensitive	Neuron1, 2, 3, 5
Na_v1.9	SCN11A	IL	−1.16	TTX-resistant
Ca²⁺ channels
Ca_v1.2	CACNA1C	CA	+0.56	L-type	Neuron1, 2, 3, 5, pericytes
Ca_v1.3	CACNA1D	CA	+0.57	L-type	Neuron1,3
Ca_v2.1	CACNA1A	CA	+0.64	P/Q-type	OPC, neuron1, 2
Ca_v2.3	CACNA1E	CA	+0.97	P/Q-type	Neuron1, 2, 5
Ca_v3.1	CACNA1G	IL	+1.8	T-type
Ca_v3.2	CACNA1H	CA	+1.12	T-type
Ca_v3.3	CACNA1I	CA	+1.03	T-type
Ryanodine
Ryr2	RYR2	CA	+0.85	Ca²⁺ Release channel	Neuron1, 2, 3
Ryr3	RYR3	IL	−0.76	Ca²⁺ Release channel	Astrocytes1
TRP channels
TRPC1	TRPC1	AL, IL, RL	−0.5 (AL); −0.48 (IL); −0.85 (RL)	Ca²⁺-permeable cation channel
TRPM2	TRPM2	IL	+0.92	Ca²⁺-permeable cation channel
TRPM3	TRPM3	IL, RL	−1.09 (IL); −0.98 (RL)	Ca²⁺-permeable cation channel	Astrocytes1, neuron1
TRPM6	TRPM6	CA, IL, RL	−0.99 (CA); −1.06 (IL); −1.08 (RL)	Ca²⁺-permeable cation channel
TRPP1	PKD2	IL	−0.48	Ca²⁺-permeable cation channel
TRPP3	PKD2L2	CA	−0.58	Ca²⁺-permeable cation channel
TRPV1	TRPV1	CA	−1.04	Ca²⁺-permeable cation channel
TRPV3	TRPV3	AL, CA, IL, RL	−0.51 (AL); −0.72 (CA); −0.5 (IL); −0.74 (RL)	Ca²⁺-permeable cation channel
TRPV5	TRPV5	AL, CA, IL, RL	−1.4 (AL); −1.67 (CA); −1.72 (IL); −2.02 (RL)	Ca²⁺-permeable cation channel
TRPV6	TRPV6	AL, CA, IL, RL, NAWM	−1.77 (AL); −1.97 (IL); −1.32 (CA); −2.23 (RL); 0.86 (NAWM)	Ca²⁺-permeable cation channel
Cl⁻ channels
CLC-2	CLCN2	CA	−0.57	Inward rectification
CLC-4	CLCN4	AL, IL, RL	−0.79 (AL); −0.73 (IL); −1.03 (RL)	Cl⁻/H⁺ antiporter
CLC-7	CLCN7	CA	−0.72	Cl⁻/H⁺ antiporter
Connexins and pannexins
Cx43	GJA1	AL, CA, RL	+1.53 (AL); +1.12 (CA); +1.19 (RL)	Monovalent and divalent ions	Astrocytes1, astrocytes2
Cx32	GJB1	AL, CA, IL, RL	−1.6 (AL); −1.5 (CA); −1.85 (IL); −2.44 (RL)	Monovalent and divalent ions	Oligo5
CX37	GJA4	IL	+1.19	Monovalent and divalent ions	Pericytes
Cx47	GJC2	AL, CA	−1.62 (AL); −1.74 (CA)	Monovalent and divalent ions
Panx1 Others	PX1	IL	+0.56	Monovalent and divalent ions
Piezo2	PIEZO2	AL, CA, IL, RL	−0.92 (AL); −1.01 (CA); −0.93 (IL); −1.49 (RL)	Ca²⁺ -permeable	Oligo1, Oligo6
CFTR	CFTR	AL, CA, IL, RL	−1.22 (AL); −1.37 (CA); −1.77 (IL); −1.86 (RL)	Cl⁻-permeable	Oligo1
H_v1	HVCN1	CA, RL	+0.71 (CA); +0.92 (RL)	H⁺-selective
Na_vi2.1	NALCN	AL, IL, RL	−0.49 (AL); −0.73 (IL); −0.88 (RL)	Sodium leak channel, non-selective
Orai3	ORAI3	AL, RL	+0.87 (AL); +1.25 (RL)	Store-Operated Ca²⁺ entry
Aquaporin 1	AQP1	CA, IL	−1.03 (CA); −0.12 (IL)	Water, ammonia, H₂0₂ permeability	Astrocytes1, astrocytes2
CATSPERG	CATSPERG	CA	+0.7	Ca²⁺ -permeable
CATSPERE	CATSPERE	IL	−0.48	Ca²⁺ -permeable

^aExpression and distribution of unique and overlapping genes coding for ion channels within chronic active (CA), active (AL), inactive (IL) remyelinating (RL) lesions, and normal-appearing white matter (NAWM). The information is based on the bulk-RNAseq (Elkjaer et al., 2019) and data are collected from the database available at www.msatlas.dk (Frisch et al., 2020).

^bCell type-specific clusters with significant expression of ion channels genes in human brain WM. The information is based on the snRNAseq from the WM of individuals with SPMS and non-neurological control subjects (Jakel et al., 2019), and data are collected from the database available at https://ki.se/mbb/oligointernodeen/ where the encoded subunits were listed according to the IUPHAR nomenclature. Fold changes of up-regulated genes are shown in bold.

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Figure 2

The expression profile of the ion channel genes uniquely expressed in different lesion types. (A) Left panel: The Venn diagram represents the number of overlapping and lesion-specific differentially expressed genes coding for ion channels in chronic active (CA), active (AL), inactive (IL), and remyelinating (RL) lesions and in normal-appearing white matter (NAWM) compared to control white matter. Right panel: The heatmap shows two genes, coding for ion channels KCNH8 and TRPV6 that are significantly altered in all lesion types compared to control white matter. Scale bar indicates fold changes. (B) The Venn diagram, the heatmap, and the scale bar show the single ion channel gene, KCNK10, which is uniquely downregulated in active lesion (AL). (C) The Venn diagram, the heatmap, and the scale bar show the eight genes coding for ion channels that are uniquely significantly differentially dysregulated in inactive lesion (IL). (D) The Venn diagram, the heatmap, and the scale bar show the 33 genes coding for ion channels that are significantly and differentially dysregulated compared to control white matter in chronic active lesion (CA). The red box in Venn diagrams marks the genes that are specifically dysregulated in the corresponding type of lesion.

Table 2

Profiling expression of unique gene in lesions in WM clusters of healthy and SPMS brain^a.

Protein	Gene	Neuron	Astrocyte	OPC	COP	ImOLG	Oligo	Microglia	Pericyte
K⁺ channels
Kv1.1	KCNA1	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d
Kv1.2	KCNA2	+	+/–	+/–	+/–	–	+/–	–	–
Kv1.4	KCNA4	+/–	–	–	–	–	–	–	–
Kv2.1	KCNB1	+	+/–	+/–	+	+/–	+/–	–	+
Kv2.2	KCNB2	++	+/–	–	+/–	+/–	+/–	–	–
Kv3.3	KCNC3	+	+/–	–	+/–	+/–	+/–	+/–	–
Kv4.2	KCND2	+++	+	++++	+++	+	+/–	+/–	+/–
Kv7.2	KCNQ2	+	+/–	+	+	+/–	+/–	–	+/–
Kv7.3	KCNQ3	+++	+	+	+	++	+/–	+++	+/–
Kv7.5	KCNQ5	++++	+	+/–	+	+	+/–	+/–	+/–
Kv8.1	KCNV1	+	–	–	+/–	+/–	–	–	–
Kv9.2	KCNS2	+	–	–	+/–	–	–	–	–
Kv10. 2/EAG2	KCNH5	+	+/–	+/–	+	+/–	+/–	–	–
Kv11.3/ERG3	KCNH7	+++	+/–	–	+	+	+/–	–	–
Kv12.1/ELK1	KCNH8	+	+++	++	+++	++	+++	+/–	+/–
TREK1	KCNK2	+	+/–	+	+/–	–	–	–	–
TREK2	KCNK10	+	+/–	+/–	+	+/–	+/–	–	–
K_Ca2.3	KCNN3	+	++	+	+	+	+/–	+/–	+/–
KNa1.1	KCNT1	+	–	–	+/–	+/–	–	–	–
Kir3.2	KCNJ6	+	+/–	+	+	–	+	–	–
Kir5.1	KCNJ16	–	+/–	+	+	–	–	–	–
Na⁺ channels
Nav1.1	SCN1A	++	+	+++	++	+	+/–	–	–
Nav1.2	SCN2A	+++	+	+/–	+	+	+/–	–	+/–
Nav1.3	SCN3A	++	+/–	++	++	+	+	–	+/–
Nav1.6	SCN8A	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d
Nav1.9	SCN11A	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d
Ca²⁺ channels
Cav1.2	CACNA1C	+++	+	+	+	+	+/–	–	+++
Cav1.3	CACNA1D	++	+/–	+	+	+	+/–	+	–
Cav2.1	CACNA1A	+++	+	+++	++	+	+/–	+	+/–
Cav2.3	CACNA1E	++	+/–	+/–	+	+	+/–	–	–
Cav3.1	CACNA1G	+	–	+/–	+/–	–	–	–	–
Cav3.2	CACNA1H	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d
Cav3.3	CACNA1I	+	–	–	+/–	–	–	–	–
Ryanodine
Ryr2	RYR2	++++	+	+/–	+	+	+	+/–	+
Ryr3	RYR3	+	+++	+	+	+	+/–	+/–	+/–
TRP channels
TRPM2	TRPM2	+	+/–	–	+/–	+	–	+	+/–
TRPP1	PKD2	+	++	+	++	++	+	+	+
TRPP3	PKD2L2	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d
TRPV1	TRPV1	+/–	+/–	–	+/–	–	+/–	–	–
TRPV6	TRPV6	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d
Cl⁻ channels
CLC−2	CLCN2	+/–	+/–	+/–	+/–	+/–	+	–	–
CLC−7	CLCN7	+	+	+	+	+	+	+	+/–
Connexins
Cx37	GJA4	–	–	–	–	–	–	–	++
Pannexin
Px1	PANX1	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d
Catsper
CATSPERG	CATSPERG	+/–	+/–	–	+/–	+/–	+/–	–	–
CATSPERE	CATSPERE	n.d	n.d	n.d	n.d	n.d	n.d	n.d	n.d

^asn-RNAseq from the white matter of individuals with SPMS and non-neurological controls. The information is based on the snRNAseq from the WM of individuals with SPMS and non-neurological control subjects (Jakel et al., 2019), and data are collected from the database available at https://ki.se/mbb/oligointernodeen/. Expression levels are based on the mean normalized expression counts (log-scale) per cluster.

+/– (log scale > 0.01 ≤ 0.1); + (log scale > 0.1 ≤ 0.5); ++ (log scale > 0.6 ≤ 1); +++ (log scale >1.1 ≤ 1.5); ++++ (log scale > 1.5); – (log scale 0); n.d., not detected; red (+), highly expressed gene in the cluster if compared to the rest of the clusters.

Note, that in the database, some of the clusters encompass both control and MS samples and, therefore, the mean can represent a combination of counts from control and MS brain.

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Figure 3

Distribution of uniquely dysregulated genes encoding ion channels in SPMS lesions. Schematic representation of active (AL), chronic active (CA), inactive (IL), and remyelinating (RL) lesions, and normal-appearing white matter (NAWM). Upregulated (blue) and downregulated (red) ion channels encoded by uniquely dysregulated genes are listed according to their expression in the lesions and in neuronal, oligodendrocyte precursor cells (OPCs), committed OPCs (COPs), oligodendrocytes (Oligo), microglia, immune oligo (ImOLG), astrocyte, pericyte, and unknown clusters. GM, gray matter; WM, white matter; v, brain ventricle. Gray areas indicate active inflammatory lesion, white areas indicate demyelinated inactive lesions, red spot indicates tissue damage, red arrow indicates axonal dysfunction. Source icon is from Biorender.com.

The goal of the present review is to discuss the current knowledge on the expression and function of ion channels that turned out to be significantly and uniquely dysregulated in WM lesions of SPMS brain. We summarize the information in the context of human MS and the related experimental models (Tables 1–3, Figure 4).

Table 3

Expression and role of unique dysregulated ion channels in experimental models of MS.

Gene/protein	Distribution, localization	Cellular functions during physiological conditions	WM in MS models
			Alterations	Role
KCNA1/K_v1.1	JPN of myelinated axons	Regulate AP propagation and neural excitability	Redistribution to internodes and nodal segments, upregulation	Hyperpolarise axonal V_rest, affect AP threshold, impair AP conduction
	Microglia, astrocyte (t), OPCs (t)	Proliferation, cell activation
KCNA2/K_v1.2	JPN of myelinated axons	Regulate AP propagation and neural excitability	Redistribution to internodes and nodal segments, upregulation	Hyperpolarise axonal V_rest, affect AP threshold, impair AP conduction
	Reactive astrocyte, microglia, OPC	Proliferation, cell activation
KCNA4/K_v1.4	Axons (HP)	Regulate AP propagation and neural excitability	Upregulation in astrocytes and OPCs around EAE lesions	Deficiency ameliorated EAE course in KO mice, but have no effect on demyelination/remyelination in the cuprizone model
	Reactive astrocyte, OPCs	Proliferation
KCNB1/K_v2.1	Soma, proximal dendrites, AIS Microglia, OPCs (t)	Influence AP duration during high frequency firing, regulate neuronal excitability	Unknown in WM Downregulation in motor neurons of GM spinal cord during EAE	Unknown
KCNB2/K_v2.2	Soma, proximal dendrites, AIS Not detected in glia	Influence AP duration during high frequency firing, regulate neuronal excitability	Unknown	Unknown
KCNC3/K_v3.3	Axons, somatodendritic compartment Astrocyte, microglia (t), OPCs (t)	Regulate AP firing at high frequency	Upregulation in some injured WM axons	Unknown
KCND2/K_v4.2	Soma, dendrites Astrocyte (t), OPCs (t), microglia (t)	Regulate threshold for AP initiation and repolarization, frequency-dependent AP broadening, AP back-propagation	Unknown	Unknown
KCNQ2/K_v7.2	AIS, nodes of Ranvier OPCs, microglia	Stabilize V_rest, regulate activity of Na_V-channels, accelerate AP upstroke, influence neuronal subthreshold excitability, regulate spike generation, and repetitive firing	Unknown	Unknown
KCNQ3/K_v7.3	AIS, nodes of Ranvier Microglia (pro-inflammatory), OPCs, astrocyte (t)	Stabilize V_rest, regulate activity of Na_V-channels, accelerate AP upstroke, influence neuronal subthreshold excitability, regulate spike generation and repetitive firing	Unknown in WM Upregulated in demyelinated neocortical axons of L5 pyramidal neurons in the cuprizone model.	Unknown in WM Ensure AP conduction in demyelinated GM axons, decrease excitability
KCNQ5/K_v7.5	Soma, dendrites Astrocyte, OPCs, microglia	Contributes to AHP currents in the HP	Unknown	Unknown
KCNV1/K_v8.1	Unknown Oligo lineage (t)	Co-assemble with K_v2.1, reduce K_v2.1 current density which may lead to AP broadening and hyper-synchronized high-frequency firing	Unknown	Unknown
KCNS2/K_v9.2	Unknown Oligo lineage (t)	Co-assemble with K_v2.1	Unknown	Unknown
KCNH5/EAG2	Unknown Astrocyte (t), OPCs (t)	Unknown	Unknown	Unknown
KCNH7/ERG3	Unknown Astrocyte (t), OPCs (t), microglia (t)	Dampen excitability, stabilize V_rest	Unknown	Unknown
KCNH8/ELK1	Unknown OPCs (t)	Unknown	Unknown	Unknown
KCNK2/TREK1	Axons, and node of Ranviers in afferent myelinated nerve Astrocyte, microglia (t) OPCs (t)	Contribute to “leak” K⁺-current, help establishing and maintaining V_rest, regulate neuronal excitability, ensure AP repolarization at nodes of Ranvier in afferent myelinated fibers Contribute to passive membrane K⁺ conductance, glutamate release	Unknown	Deficiency aggravates EAE course in KO mice Channel activation reduces CNS immune cell trafficking across BBB and attenuate EAE course
KCNK10/TREK2	Unknown Astrocyte OPCs (t)	Contribute to “leak” K⁺-current, help establishing and maintaining V_rest Contribute to K⁺ buffering, glutamate clearance	Unknown	Unknown
KCNT1/K_Na1.1	Soma, axons Astrocytes (t)	Regulate the generation of slow afterhyperpolarization, firing patterns, and setting and stabilizing the V_rest	Unknown	Unknown
KCNN3/K_Ca2.3	Dendrites, AIS Astrocyte, microglia, oligo lineage (t)	Regulate AP propagation and neuronal excitability, contribute to maintaining Ca²⁺-homeostasis K⁺ buffering in astrocytes Microglia proliferation and cytokines production	Unknown	Unknown
KCNJ6/K_ir3.2	Somatodendritic compartment Astrocyte, oligo lineage (t)	K⁺-homeostasis, maintenance of V_rest, hyperpolarization, control of AP firing and neuronal excitability, inhibition of excitatory neurotransmitter release	Unknown	Unknown
KCNJ16/K_ir5.1	Somatodendritic compartment, dendritic spines Astrocyte, oligo lineage, microglia (t)	Silent channel when combined with K_ir2.1. When combined with K_ir4.1, build channels with larger conductance and greater pH-sensitivity. Plays a role in synaptic transmission Chemoreception K⁺ buffering	Unknown	Unknown
SCN1A/Na_v1.1	Somatodendritic compartment, AIS, nodes of Ranvier Microglia, astrocyte, OPCs (t)	Saltatory conduction, maintenance of sustained firing, control of excitability Microglia phagocytosis, cytokine release	Increase or no change; localize along the demyelinated regions	Unknown
SCN2A/Na_v1.2	AIS, immature nodes of Ranvier, along the non-myelinated axons Astrocyte, pre-oligodendrocytes	Back-propagation of AP into the somatodendritic compartment, may support slow spike propagation Oligo maturation	Increase of diffuse distribution along demyelinated axons in various mouse models; no change in myelin-deficient rat Upregulated in astrocytes during EAE	Unclear. Suggested: preservation of AP propagation, or axonal damage
SCN3A/Na_v1.3	Somatodendritic compartment, along the axons including myelinated fibers Astrocyte oligo lineage (t)	AP initiation and propagation, proliferation and migration of cortical progenitors	No change in the optic nerve	Unknown
SCN8A/Na_v1.6	AIS, nodes of Ranvier; low density on cell soma, dendritic shafts, synapses Astrocyte, microglia oligo (t)	AP initiation and propagation, neuronal excitability	Decrease at the nodes of Ranvier, increase of diffuse distribution along the damaged axons, no change at AIS Upregulated in microglia/macrophages during EAE	May trigger Na⁺ increase in axoplasm, reversal of NCX, and intra-axonal Ca²⁺ overload. Deletion improves axonal health during EAE
SCN11A/Na_v1.9	Soma, proximal processes Negligible in all glial cells (t)	Regulate excitation, control activity-dependent axonal elongation, mediate sustained depolarizing current upon activation of muscarinic receptors	Unknown	Unknown
CACNA1C/Ca_V1.2	Somatodendritic compartment (synaptically, extrasynaptically), axons, axonal terminals (extrasynaptically), pioneer axons during development Astrocyte, oligo lineage, reactive microglia	Synaptic modulation, propagation of dendritic Ca²⁺ spikes, regulation of glutamate receptor trafficking, CREB phosphorylation, coupling of excitation to nuclear gene transcription, modulation of long-term potentiation, neurites growth and axonal pathfinding during development Astrogliosis OPCs development and myelination	Unknown	Unknown. Suggested: Neurodegeneration because L-type VGCCs blockers attenuate mitochondrial pathology in nerve fibers and axonal loss Deletion in astrocyte- reduces cell activation and pro-inflammatory mediators release in the cuprizone model Deletion in OPCs reduced remyelination in the cuprizone model
CACNA1D/Ca_V1.3	Somatodendritic compartment, axonal cylinders Astrocyte, microglia oligo lineage	Pacemaking activity, spontaneous firing, Ca²⁺-dependent post-burst after-hyperpolarization, Ca²⁺-dependent intracellular signaling pathways, regulation of morphology of dendritic spines and axonal arbores Oligodendrocyte-axon signaling, release of pro-inflammatory mediators by microglia	Unknown	Unknown. Suggested: neuroprotection because L-type VGCCs blockers attenuate mitochondrial pathology in nerve fibers and axonal loss
CACNA1A/Ca_V2.1	Axonal synaptic terminals, axonal shafts in WM, somatodendritic compartment Reactive astrocyte OPCs, premyelinating oligo, microglia (t)	Neurotransmitter release at neuronal and neuron-glia synapses, regulation of BK and SK channels, control of neuronal firing, regulation of gene expression, local Ca²⁺ signaling, and cell survival Calcium influx in oligo upon neuronal activity	Unknown	Unknown
CACNA1E/Ca_V2.3	Dendritic spines, axonal terminals Astrocyte, oligodendrocyte	Neurotransmitter release, synaptic plasticity, regulation of BK, SK, and K_V4.2 channels	Unknown	Unknown
CACNA1G/Ca_V3.1	Somatodendritic compartment, AIS Astrocyte (t) oligo lineage	Generation and timing of APs, regulation of neuronal excitability, rhythmic AP bursts in thalamus, neuronal oscillations, neurotransmitter release	Unknown	T-cells from KO mice show decreased cytokine release Deficiency in KO mice inhibits the autoimmune response in the EAE model
CACNA1H/Ca_V3.2	Somatodendritic compartment, AIS Astrocyte oligo lineage	Generation and timing of APs, regulation of neuronal excitability, rhythmic AP bursts in thalamus, neuronal oscillations, neurotransmitter release	Unknown	Unknown
CACNA1I/Ca_V3.3	Somatodendritic compartment	Generation and timing of APs, regulation of neuronal excitability, rhythmic AP bursts in thalamus, neuronal oscillations, neurotransmitter release	Unknown	Unknown
RyR2	Along ER (also in axons) Astrocyte, oligo lineage	Ca²⁺ release from the ER into the cytoplasm, vesicle fusion, neurotransmitter release, synaptic plasticity, growth cone dynamics	Unknown	Unknown
RyR3	Along ER (also in axons) Astrocyte, OPCs, oligodendrocytes	Ca²⁺ release from the ER into the cytoplasm, vesicle fusion, neurotransmitter release, synaptic plasticity, growth cone dynamics Astrocyte motility OPCs development	Unknown	Unknown
TRPV1	Soma, post-synaptic dendritic spines, synaptic vesicles Astrocyte, microglia, oligodendrocytes	Regulation of Ca²⁺-signaling, synaptic plasticity Astrocyte: migration, chemotaxis, activation during stress, inflammasome activation Microglia: migration, cytokine production, ROS generation, phagocytosis, polarization, cell death	Suggested a main role in regulating microglia inflammatory response	Both detrimental and beneficial effects have been described in EAE disease
TRPV6	Unknown Astrocyte (t)	Unknown	Unknown	Unknown
TRPM2	Soma and neurites in neuronal cultures Microglia, astrocyte (t), oligodendrocyte (t)	Contribute to synaptic plasticity and play an inhibitory role in neurite outgrowth Microglia activation and generation of proinflammatory mediators	Upregulated in monocyte-lineage cells	TRPM2 deficiency reduce monocyte infiltration in EAE
PKD2/TRPP1	ER, primary cilia, and plasma membrane Astrocyte (t), microglia (t), oligo lineage (t)	Maintenance of Ca²⁺-homeostasis, cell proliferation	Unknown	Unknown
PKD2L2/TRPP3	Unknown Astrocyte (t), microglia (t)	Unknown	Unknown	Unknown
CLCN2/CLC-2	Plasma membranes, intracellular membranes Astrocyte, OPCs, microglia	Maintenance of low intracellular Cl⁻ level, control of cell volume homeostasis, regulation of GABA_AR-mediated synaptic inputs, regulation of neuronal excitability Interacts with AQP4 in astrocytes, regulates OPCs differentiation, contribute to volume regulation and phagocytosis in microglia	Unknown	Unknown
CLCN7/CLC-7	Lysosomes Microglia, astrocyte (t), oligo lineage (t)	Suggested function in the neuronal endo-lysosomal pathway Regulate lysosomal acidification in activated microglia	Unknown	Unknown
GJA4/CX37	Largely expressed in vascular cells	Regulate vasomotor activity, endothelial permeability, and maintenance of body fluid balance	Unknown	Unknown
PANX1/Px1	Soma, dendrites, axons Astrocyte, OPCs microglia	Paracrine and autocrine signaling, ATP-sensitive ATP release in complex with P2X₇Rs, intercellular propagation of Ca²⁺-waves, cell differentiation, migration, synaptic plasticity, memory	Unknown	Panx-1 induced ATP release and inflammasome activation contribute to WM damage during EAE Inhibition of Panx1 using pharmacology or gene disruption delays and attenuates disease course in EAE and cuprizone model
CATSPERG	Unknown Oligo lineage (t) Microglia (t)	Unknown	Unknown	Unknown
CATSPERE	Unknown	Unknown	Unknown	Unknown

AHP, afterhyperpolarization; AIS, axon initial segment; AP, action potential; BK, big-conductance Ca²⁺-activated K⁺-channels; ER, endoplasmatic reticulum; GABA_AR, ionotropic gamma aminobutyric acid A receptor; HP, hippocampus; JPN, juxtaparanodal regions; NCX, Na⁺/Ca²⁺ exchanger; SCI, spinal cord injury; SK, small-conductance Ca²⁺-activated K⁺-channels; SSCx, somatosensory cortex; t, transcipts; V_rest, resting membrane potential.

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Figure 4

Putative roles of ion channels encoded by uniquely dysregulated genes in SPMS lesions. Schematic illustration of the putative detrimental (red box), putative beneficial (blue box), and unexplored (gray box) functional roles of ion channel encoded by the uniquely dysregulated genes in active (AL), chronic active (CA), inactive (IL), and remyelinating (RL) lesions, and normal-appearing white matter (NAWM) of SPMS brain. Source icon is from Biorender.com.

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K⁺ Channels

Glia

KCNQ3 gene is expressed in spinal cord WM astrocytes (Devaux et al., 2004), while KCNQ5 is expressed in rat retinal astrocytes (Caminos et al., 2015). The KCNQ2-5 mRNAs and proteins were detected in rat cortical OPCs and microglia cultures, while differentiated oligodendrocytes showed weak KCNQ4 expression (Wang et al., 2011; Vay et al., 2020).

Expression and Function in MS

Bulk RNA-seq found upregulation of KCNQ2-3-5 transcripts in CA lesions (Figure 2, Table 1; Elkjaer et al., 2019; Frisch et al., 2020). The snRNA-seq reported KCNQ2-3-5 expression in neuronal clusters and KCNQ3 expression in immune oligodendroglia (ImOLG) and microglia/macrophages clusters (Tables 1, ,2;2; Jakel et al., 2019). K_v7.3 upregulation may reflect increased necessity of the channels along the axons because K_v7.3 subunit extensively redistributes to internodes of acutely and chronically demyelinated GM axons in the cuprizone model (Hamada and Kole, 2015). It is tempting to speculate that K_v7 upregulation may be beneficial during MS. First, K_v7 channels may increase the availability of transient Na_v current via membrane hyperpolarization supporting AP conduction in demyelinated axons (Battefeld et al., 2014). Second, K_v7 channels may mitigate inflammation-induced neuronal excitability because, following LPS exposure, the I_M inhibition underlies hyperexcitability of hippocampal neurons that is reversed by a nonselective K_v7-opener retigabine (Tzour et al., 2017). Although retigabine also exerts neuroprotective effects in several neurodegenerative conditions (Boscia et al., 2006; Nodera et al., 2011; Wainger et al., 2014; Bierbower et al., 2015; Li et al., 2019; Vigil et al., 2020; Wu et al., 2020), a clinical trial with retigabine analog flupirtine failed to demonstrate neuroprotective effects during MS (Dorr et al., 2018). Furthermore, blockade of K_v7 channels with XE-991 inhibited migration of LPS-treated pro-inflammatory microglia in vitro (Vay et al., 2020), suggesting that these channels may promote the pro-inflammatory role of microglia also during MS. Hence, neuronal and glial K_v7 channels may have diverse functions during MS.

K_v8.1 and K_v9.2 (KCNV1 and KCNS2)

Neurons

KCNV1 and KCNS2 genes encode for electrically silent (K_vS) K_v8.1- and K_v9.2 subunits that assemble into hetero-tetrameric channels with K_v2 subunits (Bocksteins, 2016). A number of channelopathies is ascribed to K_vS subunits (Salinas et al., 1997a; Liu et al., 2016; Allen et al., 2020), pointing to their important physiological role.

Glia

KCNV1 and KCNS2 transcripts were found in oligodendrocyte lineage cell (Marques et al., 2016).

Expression and Function in MS

Bulk RNA-seq showed upregulation of KCNV1 and KCNS2 genes in CA lesions (Figure 2, Table 1; Elkjaer et al., 2019; Frisch et al., 2020). The snRNA-seq detected KCNV1 and KCNS2 in neuronal clusters (Table 2; Jakel et al., 2019). Co-assembly between K_v8.1 and K_v2.1 reduces K_v2.1 current density (Hugnot et al., 1996; Castellano et al., 1997): the high stoichiometry of the K_v8.1 subunit suppresses surface expression and favors retention of heteromeric channels in the ER (Salinas et al., 1997b). Neurons with reduced K_v2.1-mediated currents demonstrate broadened APs (Du et al., 2000) underlying hyper-synchronized high-frequency firing observed during epilepsy. Hence, upregulated K_vS subunits in CA lesions may influence the localization of clustered K_v2 subunits in SPMS brain and affect AP firing and/or propagation.

Eag2, erg3, and elk1 (KCNH5, KCNH7, and KCNH8)

KCNH genes encode for K_v10–K_v12 subfamilies, all orthologs of the Drosophila ether-àgo-go (EAG) channels. They include two eag (K_v10), three eag-related (erg/K_v11), and three eag-like (elk/K_v12) K⁺ channels that can form heteromeric channels within each subfamily (Rasmussen and Trimmer, 2019).

Neurons

All EAG channels are expressed in the CNS neurons (Ludwig et al., 2000; Papa et al., 2003; Zou et al., 2003), but only erg-mediated currents have been verified using suitable blockers (Bauer and Schwarz, 2018).

Glia

RNA-seq detected KCNH5, KCNH7, and KCNH8 expression in mouse OPCs (Falcao et al., 2018). KCNH5 and KCNH7 genes were found in astrocytes (Batiuk et al., 2020), while only the KCNH7 gene was detected in mouse microglia (Hammond et al., 2019). Erg-type currents were reported in neopallial microglia cultures (Zhou et al., 1998) and hippocampal astrocytes (Emmi et al., 2000; Papa et al., 2003).

Expression and Function in MS

Bulk RNA-seq detected increased KCNH5(eag2) and KCNH7(erg3) transcripts in CA lesions and downregulation of KCNH8(elk1) transcript in all lesions and NAWM (Figure 2, Table 1; Elkjaer et al., 2019; Frisch et al., 2020). The snRNA-seq found significant expression of KCNH5 and KCNH7 transcripts in neuronal clusters and KCNH8 in mature oligodendrocyte clusters (Tables 1, ,2;2; Jakel et al., 2019). The functional role of eag2, erg3, and elk1 during MS may be related to altered neuronal excitability. Indeed, human eag1 and eag2 gain-of-function mutations underlie severe neurological disorders associated with epileptic seizures (Allen et al., 2020). The erg channels that are active at subthreshold potentials stabilize the V_rest and dampen excitability (Fano et al., 2012). Erg3 knockdown in mice increases intrinsic neuronal excitability and enhances seizure susceptibility, while treatment with erg activator reduces epileptogenesis (Xiao et al., 2018). Erg3 expression is decreased in the brain of epilepsy patients. Remarkably, association of KCNH7(erg) intronic polymorphisms with MS pathogenesis was speculated although never substantiated (Martinez et al., 2008; Couturier et al., 2009).

Two-Pore Domain K⁺ Channels (K2P)

K2P K⁺ channels are encoded by 15 KCNK genes, stratified into six subfamilies: TWIK, TASK (TWIK-related acid-sensitive), TREK (TWIK-related arachidonic acid activated), THIK (tandem pore domain halothane-inhibited), TALK (TWIK-related alkaline pH-activated), and TRESK (TWIK-related spinal cord) K⁺ channels (Enyedi and Czirjak, 2010). K2P K⁺ channels contribute to “leak” K⁺ current, helping to establish and maintain V_rest (Enyedi and Czirjak, 2010).

TREK1 and TREK2 (KCNK2 and KCNK10)

Neurons and Glia

KCNK2 and KCNK10 genes encode for TREK-1 and TREK-2 channels, which are expressed in neurons, astrocytes, and OPC (Hervieu et al., 2001; Talley et al., 2001; Falcao et al., 2018). Only TREK-1 transcripts were detected in microglia (Hammond et al., 2019). In astrocytes, TREK channels contribute to passive conductance and glutamate release (Zhou et al., 2009; Woo et al., 2012). TREK-1 and TREK-2 may be activated by a wide range of physiological and pathological stimuli reminiscent of inflammatory environment including membrane stretch, heat, intracellular acidosis, and cellular lipids (Ehling et al., 2015).

Expression and Function in MS

Bulk RNA-seq found upregulated TREK-1 transcripts in CA lesions, but a divergent modulation was observed for TREK-2 mRNAs in ALs (Figure 2, Tables 1, ,2;2; Elkjaer et al., 2019; Frisch et al., 2020). KCNK2 and KCNK10 transcripts were detected in neuronal and oligodendrocyte clusters, but scarcely observed in astrocytes (Table 2; Jakel et al., 2019). TREK-1 upregulation in CA lesions most likely reflects a protective response because TREK-1 plays a neuroprotective role during neurological diseases, including MS (Djillani et al., 2019). TREK-1 reduces neuronal excitability by hyperpolarizing the membrane potential (Honore, 2007) and is required for rapid AP repolarization at the node of Ranvier in mammalian afferent myelinated nerves, while TREK-1 loss-of-function retards nerve conduction and impairs sensory responses in animals (Kanda et al., 2019). Treatment of mice with TREK-1 activators, riluzole (Gilgun-Sherki et al., 2003), or alpha-linolenic acid attenuates EAE course (Blondeau et al., 2007), while these effects are reduced in TREK-1^−/− mice (Bittner et al., 2014). TREK-1 function is also important for non-neuronal cells because aggravated EAE course in TREK-1^−/− mice is associated with increased numbers of infiltrating T cells and higher endothelial expression of ICAM1 and VCAM1 (Bittner et al., 2013), and TREK-1 is reduced in the microvascular endothelium in inflammatory MS brain lesions (Bittner et al., 2013).

Voltage-Gated Ca²⁺ Channels (VGCCs)

The VGCCs are composed of α1-, β-, α2/δ-, and γ-subunits (Catterall, 2011; Zamponi et al., 2015). The pore-forming α1-subunit determines channel activity, whereas other subunits are auxiliary and regulate function of α1-subunit. In mammalian cells, 10 different α1-subunits, encoded by different genes, classify into three subfamilies: Ca_V1, Ca_V2, and Ca_V3 (Catterall, 2011; Zamponi et al., 2015; Alves et al., 2019). Depending on the pharmacological properties and activation voltage of Ca²⁺ currents, five different types of VGCCs are distinguished: L-type, N-type, P/Q-type, R-type, and T-type.

L-Type VGCCs

The α1-subunit of L-type VGCCs is encoded by CACNA1S (Ca_V1.1), CACNA1C (Ca_V1.2), CACNA1D (Ca_V1.3), or CACNA1F (Ca_V1.4) genes. High sensitivity to dihydropyridine modulators distinguishes L-type Ca²⁺ channels from other types of VGCCs. In the CNS, mainly Ca_V1.2 and Ca_V1.3 subunits are expressed (Lipscombe et al., 2004; Zamponi et al., 2015), but Ca_V1.1 subunit was detected in human and rat basal ganglia where it is co-expressed with RyRs in GABAergic neurons (Takahashi et al., 2003).

Ca_V1.2 (CACNA1C)

Neurons

Ca_V1.2 channels account for 89% of all Ca²⁺ currents mediated by L-type VGCCs in the brain (Alves et al., 2019; Enders et al., 2020). In hippocampal neurons, Ca_V1.2 channels localize to somatodendritic compartment being placed at synapses or extra-synaptically (Joux et al., 2001; Hoogland and Saggau, 2004; Obermair et al., 2004; Tippens et al., 2008; Ortner and Striessnig, 2016), as well as to axons and/or extrasynaptic regions of axonal terminals (Tippens et al., 2008). Within the WM, Ca_V1.2 channels were identified in the developing rat pioneer axons and the follower axons projecting through the optic nerve, corpus callosum, anterior commissure, lateral olfactory tract, corticofugal fibers, thalamocortical axons, and the spinal cord (Ouardouz et al., 2003; Huang et al., 2012).

Bulk RNA-seq revealed upregulation of Ca_v3.2 and Ca_v3.3 genes in CA lesions and upregulation of Ca_v3.1 in ILs (Elkjaer et al., 2019; Frisch et al., 2020; Table 1). The snRNA-seq detected Ca_v3.1and Ca_v3.3 transcripts in neuronal clusters, while it did not detect the Ca_v3.2 (Jakel et al., 2019; Tables 1, ,2).2). Genome-wide sequencing identified significant association of a Ca_v3.2 mutation (CACNA1Hp.R1871Q) with patients suffering relapsing-remitting MS (Sadovnick et al., 2017). Ca_v3 upregulation in MS lesions may be triggered by inflammatory mediators and may contribute to axonal dysfunction. Indeed, prostanoids and hydrogen sulfide modulate Ca_v3.2 expression and function, and increased Ca_v3.2 channel activity and axonal accumulation is associated with inflammation and pain (Sadovnick et al., 2017; Chen et al., 2018). T-type currents contribute to Ca²⁺-mediated injury of spinal cord WM axons triggered by anoxia (Imaizumi et al., 1999) and to peripheral nerve injury (Watanabe et al., 2015). L/T-type VGCC blocker lomerizine prevents retinal ganglion cell death after diffuse axonal injury (Karim et al., 2006).

Animal studies suggest that Ca_v3.1 upregulation in IL, a lesion type with complete demyelination and substantial axonal loss, may play a detrimental role. Specifically, the Ca_v3.1-deficient mice are markedly resistant to EAE induction, and this effect may be mediated by lower production of granulocyte–macrophage colony-stimulating factor (a cytokine implicated in EAE susceptibility) by CNS-infiltrating Th1 and Th17 cells (Wang et al., 2016). The Ca_v3.1 subunit is a functionally predominant T-type channel in CD4⁺ T cells (Trebak and Kinet, 2019). The Ca_v3.1-mediated Ca²⁺ increase is critical for calcineurin-NFAT activation driving transcription of cytokines in T cells, and T cells from Ca_v3.1-deficient mice show decreased IL-17A, IL-17F, and IL-21 production. The development of isoform-specific modulators should help in establishing the differential role of Ca_v3 subtypes in MS lesions.

Ryanodine Receptors

RyRs encompass three mammalian isoforms, RyR1–3, which form homo-tetrameric channels on the ER. RyRs are highly conductive Ca²⁺ channels: they get activated by Ca²⁺ influx upon plasma membrane depolarization mediating CICR from the ER (Fill and Copello, 2002; Lanner et al., 2010). In the brain, the RyR2s show predominant expression, followed by RyR3s, and then RyR1s (McPherson and Campbell, 1990; Giannini et al., 1995).

RyR2 and RyR3

Neurons

RyRs localize along ER of neurons, including WM axons (Giannini et al., 1995). They play a role in vesicle fusion, neurotransmitter release, synaptic plasticity, and growth cone dynamics (Giannini et al., 1995; Kushnir et al., 2018). RyRs form complexes with L-type Ca²⁺ channels: RyR1-Ca_v1.2 and RyR2-Ca_v1.3 (Ouardouz et al., 2003). WM axons transduce membrane depolarization to Ca²⁺ release from ER, whereby L-type VGCCs gate RyRs, analogous to “excitation–contraction coupling” in muscles (Ouardouz et al., 2003; Stirling and Stys, 2010). Genetic mutations or oxidative stress can render RyRs leaky to Ca²⁺ and promote defective signals as observed in neurodegenerative disorders, heart failure, and muscular dystrophy (Kushnir et al., 2018).

Glia

RYR2 and RYR3 transcripts, but only RyR3 protein, were found in cultured astrocytes from mouse brain (Matyash et al., 2002; Kesherwani and Agrawal, 2012). RyR2 transcripts and proteins were upregulated in spinal WM astrocytes after hypoxic injury (Kesherwani and Agrawal, 2012) and SCI (Liao et al., 2016; Pelisch et al., 2017). All RYRs subunits were found in rat optic nerve oligodendrocyte cultures (Ruiz et al., 2010), but RYR3 was selectively expressed in rat cortical OPCs (Haak et al., 2001; Li T. et al., 2018). RyR3s amplify small inward Ca²⁺ currents in astrocytes and OPC, regulating behavior of these cells (Simpson et al., 1998; Matyash et al., 2002; Haberlandt et al., 2011). RyRs mediate stress response in oligodendrocytes, and RyR inhibition attenuated intracellular Ca²⁺ overload following AMPA excitotoxicity (Ruiz et al., 2010). RyR1 and RyR2 mRNAs were detected in adult human microglia, whereas only RyR3 was found in fetal microglia (Klegeris et al., 2007). RNA-seq did not detect RYR2 and RYR3 in mouse microglia (Hammond et al., 2019).

Expression and Function in MS

Bulk RNA-seq found upregulation of RyR2 transcripts in CA lesions and downregulation of RyR3 in ILs (Table 1; Elkjaer et al., 2019; Frisch et al., 2020). The snRNA-seq revealed significant expression of RyR2 in neuronal clusters and of RyR3 in the astrocyte1 cluster (Table 1; Jakel et al., 2019). RyR subunits probably play a differential role in perturbed intracellular Ca²⁺ homeostasis in WM cells of SPMS brain. RyR2 in CA lesions may contribute to axonal dysfunction because intra-axonal Ca²⁺ overload mediated by RyRs and IP3Rs activates the mitochondrial permeability transition pore and contributes to axonal dieback and degeneration following WM ischemic injury (Ouardouz et al., 2003; Stirling and Stys, 2010; Kesherwani and Agrawal, 2012) and SCI (Stirling et al., 2014; Liao et al., 2016). The RyRs inhibitor ryanodine significantly attenuates mitochondrial dysfunction (Villegas et al., 2014), axonal dieback, and secondary axonal degeneration in injured WM (Thorell et al., 2002; Stirling et al., 2014; Orem et al., 2017). In line, mice with RyR2 gain-of-function mutation exhibit more axonal damage than wild-type controls following SCI (Stirling et al., 2014), while RyR2 knockdown attenuates mitochondrial dysfunction and ER stress and improves functional recovery (Liao et al., 2016).

Functional RyR3s may contribute to astrocyte migration in response to injury, which is important for tissue remodeling and wound healing. In fact, RyR3s control astrocyte motility because astrocytes from RyR3 KO mice display reduced migratory activity (Matyash et al., 2002). Conversely, RyR3 downregulation in ILs may influence the formation of dense astrocytic scar imposing a major barrier to axonal and myelin regeneration. RyR3s also contribute to intracellular Ca²⁺ transients during OPCs differentiation, while RyR3 inhibition prevents OPCs development (Li T. et al., 2018). Interaction between RyRs and NCX in oligodendrocyte processes may represent an amplification mechanism to generate Ca²⁺ transients required for oligodendrocyte differentiation in vitro (Casamassa et al., 2016; Hammann et al., 2018; de Rosa et al., 2019; Boscia et al., 2020). However, it remains unclear whether these mechanisms play a role in human MS. The development of selective modulators will help to establish function of RyRs in MS.

TRP Channels

Transient receptor potential (TRP) channels are tetrameric non-selective cation channels which encompass 30 different types (Nilius and Owsianik, 2011). Upon TRP channel activation, the membrane potential depolarizes, leading to activation or inactivation of voltage-gated ion channels and regulation of Ca²⁺ signaling (Gees et al., 2010). Various intracellular or extracellular stimuli, including chemical and osmotic stress, can trigger activation of TRP channels (Clapham, 2003). TRP channels are involved in pain, regulation of neurotransmitter release, and immune functions. Vanilloid TRP channels (TRPV), melastatin TRP channels (TRPM), and polycystin TRP channels (TRPP) have been detected in WM lesions of patients with progressive MS.

TRPV1

Neurons

In the CNS, TRPV1 channels are mainly localized on cell bodies and dendritic spines, but also in synaptic vesicles (Goswami et al., 2010). TRPV1 channels are activated by exogenous (i.e., capsaicin) or endogenous (i.e., high temperatures, acid pH, anandamide, 2-arachidonoylglycerol, and lipid metabolites) stimuli (Van Der Stelt and Di Marzo, 2004). They play a role in weight, appetite, and energy homeostasis (Derbenev and Zsombok, 2016; Christie et al., 2018); synaptic plasticity (Gibson et al., 2008; Wang et al., 2020); neuropathic pain (Rivat et al., 2018); and regulation of inflammatory response (Kong et al., 2017).

Glia

TRPV1 channels are expressed in astrocytes (Ho et al., 2014), microglia (Sappington and Calkins, 2008), and, to a lesser extent, oligodendrocytes (Gonzalez-Reyes et al., 2013; Marques et al., 2016).

Expression and Function in MS

Bulk RNA-seq showed significant TRPV1 downregulation in CA lesions (Figure 2, Table 1; Elkjaer et al., 2019; Frisch et al., 2020), while snRNA-seq barely detected TRPV1 (Table 2; Jäkel and Williams, 2020). The downregulated TRPV1 in CA lesions may influence neural plasticity and glia response both in the hypocellular inactive demyelinated core and in the hypercellular rim filled with activated glia. However, it is unclear whether dysfunctional TRPV1 has pro- and anti-inflammatory roles, and whether it favors or prevents CA lesion expansion and progression, because experimental findings are inconsistent. In rodents, administration of TRPV1 agonists reduced EAE severity (Tsuji et al., 2010), while the TRPV1 antagonist capsazepine, although ineffective for EAE severity (Paltser et al., 2013), reversed the beneficial effects of the endocannabinoid uptake inhibitor (Cabranes et al., 2005). Beneficial effects of TRPV1 may be mediated by its ability to promote micro-vesicle release from microglia, which enhances glutamatergic transmission in neurons (Marrone et al., 2017). However, on the other hand, TRPV1 stimulation induces the pro-inflammatory phenotype of microglia while downregulation promotes the anti-inflammatory phenotype (Hassan et al., 2014; Marrone et al., 2017). TRPV1 also regulates microglia migration, cytokine production, ROS generation, phagocytosis, and death (Kim et al., 2006; Schilling and Eder, 2009; Miyake et al., 2015). Furthermore, TRPV1 mediates migration and chemotaxis of astrocytes, their activation during stress and injury (Ho et al., 2014), and inflammasome activation. The picture becomes even more complex because TRPV1-KO mice show higher lethality during EAE peak but better recovery in the chronic stage (Musumeci et al., 2011). In addition, genetic deletion of TRPV1 in mice resulted in significant protection in the MOG-EAE model, and less severe breakdown of BBB (Paltser et al., 2013). Interestingly, patients with severe MS progression show over-representation of single-nucleotide polymorphisms (SNPs) in the TRPV1 gene (Paltser et al., 2013) that can affect the expression and activity of the channel and cortical excitability, and modulate pain (Xu H. et al., 2007; Mori et al., 2012; Stampanoni Bassi et al., 2019).

TRPV6

TRPV6 channels are distinguished by high Ca²⁺ selectivity (van de Graaf et al., 2006) and constitutive activity at low intracellular Ca²⁺ levels and V_rest (Vennekens et al., 2000). TRPV6 channels can form homo- or hetero-tetramers. TRPV5–6 are mainly expressed in epithelial and bone cells (Hoenderop et al., 2003).

Neurons and Glia

In the mouse brain, TRPV6 channels are expressed in neurons, while transcripts were detected in astrocytes by RNA-seq (Riccio et al., 2002; Nijenhuis et al., 2003; Batiuk et al., 2020).

Expression and Function in MS

Bulk RNA-seq found TRPV6 downregulation in all MS lesion types and in NAWM (Figure 2, Table 1; Elkjaer et al., 2019; Frisch et al., 2020), but snRNA-seq failed to detect TRPV6 transcripts (Table 2; Jakel et al., 2019). Little is known about the functional role of TRPV6 in brain cells. However, TRPV6 deletion in trophoblasts correlates with altered extracellular matrix (ECM) formation in the labyrinth during pregnancy (Winter et al., 2020). Hence, it will be important to investigate whether TRPV6 downregulation contributes to ECM alterations observed in SPMS lesions and believed to be a key remyelination-inhibiting factor.

Bulk RNA-seq revealed significant GJA4 upregulation in ILs (Elkjaer et al., 2019; Frisch et al., 2020), while snRNA-seq showed high GJA4 expression in pericyte cluster (Jakel et al., 2019; Tables 1, ,2).2). In chronically demyelinated axons, as those within ILs, hypoxia due to imbalance between increased energy demand and reduced ATP production because of mitochondrial dysfunction may drive angiogenesis. However, while providing trophic factors for tissue remodeling, angiogenesis may contribute to hypoperfusion and neurovascular uncoupling (Girolamo et al., 2014). Interestingly, Cx37 knockdown with siRNA in human umbilical vein endothelial cells diminishes capillary branching (Gartner et al., 2012), but Cx37^−/− mice develop a more extensive vasculature under ischemic conditions and show enhanced recovery after hind limb ischemia (Fang et al., 2011). In the future, it will be important to investigate whether Cx37 protein contributes to aberrant cerebrovascular and angiogenic responses in human ILs during MS.

Pannexins

The Pannexin (Px) family consists of three members, encoded by Panx1, Panx2, and Panx3 genes. Pannexins do not form GJ in vivo but operate as plasma membrane channels (pannexons) and participate in paracrine and autocrine signaling in brain GM and WM (Sosinsky et al., 2011; Sahu et al., 2014; Dahl, 2015).

Px1 (PANX1)

Px1 is permeable to anions, some negatively charged molecules (glutamate, aspartate, and ATP), and fluorescent dyes (Ma et al., 2012; Yeung et al., 2020). Opening of Px1 may be promoted by voltage, increased intracellular Ca²⁺, mechanical stress, extracellular K⁺, oxygen deprivation, caspases cleavage, ATP binding to P2Y or P2X₇ receptors, activation of α1-adrenergic, NMDA, and thromboxane receptors (Chiu et al., 2018; Dahl, 2018; Whyte-Fagundes and Zoidl, 2018).

Neurons and Glia

Px1 is distributed in GM and WM regions, including cerebellum, corpus callosum, and fimbria fornix of mice (Bruzzone et al., 2003) and rats (Vogt et al., 2005). Px1 is expressed in neurons, astrocytes, microglia, oligodendrocytes, vascular cells, and peripheral immune cells (Iglesias et al., 2009; Swayne et al., 2010; Orellana et al., 2013; Good et al., 2018; Lapato and Tiwari-Woodruff, 2018). In neurons, Px1 may be co-expressed with Px2 and is found in cell soma, dendrites, and axons (Cone et al., 2013).

Interaction between Px1 and purinergic signaling deserves special attention because Px1 forms complexes with P2X₇Rs (Taruno, 2018). Binding of ATP to P2X₇R triggers opening of Px1 channels with subsequent ATP release (Locovei et al., 2007; Iglesias et al., 2008; Pelegrin et al., 2008; Chiu et al., 2018). ATP signaling involving Px1 channels regulates neurite outgrowth and synaptic plasticity in neurons, while in glia, it underlies intercellular propagation of Ca²⁺ waves, cell differentiation, and migration (Giaume et al., 2021).

Expression and Function in MS

Bulk RNA-seq showed significant PANX1 upregulation in ILs (Table 1; Elkjaer et al., 2019; Frisch et al., 2020), but snRNA-seq did not detect PANX1 transcripts (Jakel et al., 2019). ILs are lesions with little/no inflammatory activity but with sharply demarcated hypocellular areas of demyelination and axonal degeneration. Px1 activation is known to enable ATP release, and ATP is a “find me” signal promoting chemotaxis of microglia/macrophages to the injury site for fast clearance of dead cells and a molecule important for myelination (Chekeni et al., 2010; Gajardo-Gomez et al., 2016). Hence, PANX1 upregulation in ILs may be a compensatory mechanism that stimulates glial activity. On the other hand, upregulated Px1 mRNA expression in cerebellum and spinal cord in chronic EAE contributes to WM damage (Lutz et al., 2013). Uncontrolled opening of P2X₇R-Px1 complex in response to demyelination triggers excessive glutamate and ATP release, altered Ca²⁺ dynamics, excitotoxicity, damage of axons, and myelin (Orellana et al., 2011; Crespo Yanguas et al., 2017). Knockout or blockade of Px1 with probenecid in rodents restrains EAE symptoms and results in reduced inflammation and decreased oligodendrocyte damage (Hainz et al., 2017), suggesting that Px1 activity supports damage during MS. More studies are required to establish how Px1 should be modulated in order to halt neurodegeneration during MS.

CatSper Channels

Catsperg and Caspere

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Glossary

Abbreviations

AIS	axon initial segment
AL	active lesion
AP	action potential
CA	chronic active lesion
Ca²⁺	calcium
Ca_V	voltage-gated calcium channels
ClC	chloride channels
CNS	central nervous system
COP	committed OPCs
Cx	connexin
EAE	experimental autoimmune encephalomyelitis
EAG	ether-àgo-go
ER	endoplasmic reticulum
GM	gray matter
HC	hemi-channel
IFN-γ	gamma-interferon
IL	inactive lesions
ImOLG	immune oligodendroglia
K2P	two-pore domain K⁺ channels
K_ir	inward rectifier potassium channel
KO	knockout
K_V	voltage-gated K⁺ channels
LPS	lipopolysaccharide
MS	multiple sclerosis
Na⁺	sodium
Na_V	voltage-gated sodium channels
NAWM	normal-appearing white matter
NCX	sodium calcium exchanger
OPCs	oligodendrocyte precursor cells
Px	pannexin
RL	remyelinating lesion
RyR	ryanodine receptor
SCI	spinal cord injury
SPMS	secondary progressive multiple sclerosis
TRP	transient receptor potential
WM	white matter.

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Footnotes

Funding. The work of FB was supported by grants from Fondazione Italiana Sclerosi Multipla FISM 2015/R/6 and by Italian Ministry for University and Research PRIN 2017, 20175SA5JJ. The work of MK was supported by Ikerbasque (Basque Foundation for Science), Spanish Ministry of Science and Innovation (Grant No. PID2019-110195RB-I00), and Basque Government. The work of ZI was supported by Lundbeckfonden R118-A11472, Scleroseforeningen R487-A33600-B15690, and R458-A31829-B15690.

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References

Abiraman K., Tzingounis A. V., Lykotrafitis G. (2018). KCa2 channel localization and regulation in the axon initial segment. FASEB J. 32, 1794–1805. 10.1096/fj.201700605R [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Absinta M., Sati P., Masuzzo F., Nair G., Sethi V., Kolb H., et al. . (2019). Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol. 76, 1474–1483. 10.1001/jamaneurol.2019.2399 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Agrawal S. K., Nashmi R., Fehlings M. G. (2000). Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal cord white matter injury. Neuroscience 99, 179–188. 10.1016/s0306-4522(00)00165-2 [Abstract] [CrossRef] [Google Scholar]
Aguado C., Garcia-Madrona S., Gil-Minguez M., Lujan R. (2016). Ontogenic changes and differential localization of T-type Ca(2+) channel subunits Cav3.1 and Cav3.2 in mouse hippocampus and cerebellum. Front. Neuroanat. 10:83. 10.3389/fnana.2016.00083 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Akhtar S., McIntosh P., Bryan-Sisneros A., Barratt L., Robertson B., Dolly J. O. (1999). A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum. Biochemistry 38, 16984–16992. 10.1021/bi992114x [Abstract] [CrossRef] [Google Scholar]
Alfaro-Ruiz R., Aguado C., Martin-Belmonte A., Moreno-Martinez A. E., Lujan R. (2019). Expression, cellular and subcellular localisation of Kv4.2 and Kv4.3 channels in the rodent hippocampus. Int. J. Mol. Sci. 20:246. 10.3390/ijms20020246 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Alix J. J., Dolphin A. C., Fern R. (2008). Vesicular apparatus, including functional calcium channels, are present in developing rodent optic nerve axons and are required for normal node of ranvier formation. J. Physiol. 586, 4069–4089. 10.1113/jphysiol.2008.155077 [Abstract] [CrossRef] [Google Scholar]
Allen N. M., Weckhuysen S., Gorman K., King M. D., Lerche H. (2020). Genetic potassium channel-associated epilepsies: clinical review of the Kv family. Eur. J. Paediatr. Neurol. 24, 105–116. 10.1016/j.ejpn.2019.12.002 [Abstract] [CrossRef] [Google Scholar]
Alrashdi B., Dawod B., Schampel A., Tacke S., Kuerten S., Marshall J. S., et al. . (2019). Nav1.6 promotes inflammation and neuronal degeneration in a mouse model of multiple sclerosis. J. Neuroinflammation 16:215. 10.1186/s12974-019-1622-1 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Alves V. S., Alves-Silva H. S., Orts D. J. B., Ribeiro-Silva L., Arcisio-Miranda M., Oliveira F. A. (2019). Calcium signaling in neurons and glial cells: role of Cav1 channels. Neuroscience 421, 95–111. 10.1016/j.neuroscience.2019.09.041 [Abstract] [CrossRef] [Google Scholar]
Arai-Ichinoi N., Uematsu M., Sato R., Suzuki T., Kudo H., Kikuchi A., et al. . (2016). Genetic heterogeneity in 26 infants with a hypomyelinating leukodystrophy. Hum. Genet. 135, 89–98. 10.1007/s00439-015-1617-7 [Abstract] [CrossRef] [Google Scholar]
Armstrong W. E., Rubrum A., Teruyama R., Bond C. T., Adelman J. P. (2005). Immunocytochemical localization of small-conductance, calcium-dependent potassium channels in astrocytes of the rat supraoptic nucleus. J. Comp. Neurol. 491, 175–185. 10.1002/cne.20679 [Abstract] [CrossRef] [Google Scholar]
Arroyo E. J., Xu T., Grinspan J., Lambert S., Levinson S. R., Brophy P. J., et al. . (2002). Genetic dysmyelination alters the molecular architecture of the nodal region. J. Neurosci. 22, 1726–1737. 10.1523/JNEUROSCI.22-05-01726.2002 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Astori S., Wimmer R. D., Prosser H. M., Corti C., Corsi M., Liaudet N., et al. . (2011). The Ca(V)3.3 calcium channel is the major sleep spindle pacemaker in thalamus. Proc. Natl. Acad. Sci. U.S.A. 108, 13823–13828. 10.1073/pnas.1105115108 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Attali B., Wang N., Kolot A., Sobko A., Cherepanov V., Soliven B. (1997). Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells. J. Neurosci. 17, 8234–8245. 10.1523/JNEUROSCI.17-21-08234.1997 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bahring R., Boland L. M., Varghese A., Gebauer M., Pongs O. (2001). Kinetic analysis of open- and closed-state inactivation transitions in human Kv4.2 A-type potassium channels. J. Physiol. 535. (Pt. 1), 65–81. 10.1111/j.1469-7793.2001.00065.x [Abstract] [CrossRef] [Google Scholar]
Bai J. Z., Lipski J. (2010). Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture. Neurotoxicology 31, 204–214. 10.1016/j.neuro.2010.01.001 [Abstract] [CrossRef] [Google Scholar]
Barron T., Kim J. H. (2019). Neuronal input triggers Ca(2+) influx through AMPA receptors and voltage-gated Ca(2+) channels in oligodendrocytes. Glia 67, 1922–1932. 10.1002/glia.23670 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Batiuk M. Y., Martirosyan A., Wahis J., de Vin F., Marneffe C., Kusserow C., et al. . (2020). Identification of region-specific astrocyte subtypes at single cell resolution. Nat. Commun. 11:1220. 10.1038/s41467-019-14198-8 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Battefeld A., Tran B. T., Gavrilis J., Cooper E. C., Kole M. H. (2014). Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons. J. Neurosci. 34, 3719–3732. 10.1523/JNEUROSCI.4206-13.2014 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bauer C. K., Schwarz J. R. (2018). Ether-a-go-go K(+) channels: effective modulators of neuronal excitability. J. Physiol. 596, 769–783. 10.1113/JP275477 [Abstract] [CrossRef] [Google Scholar]
Bekar L. K., Loewen M. E., Cao K., Sun X., Leis J., Wang R., et al. . (2005). Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes. J. Neurophysiol. 93, 1699–1709. 10.1152/jn.00850.2004 [Abstract] [CrossRef] [Google Scholar]
Bender K. J., Trussell L. O. (2009). Axon initial segment Ca2+ channels influence action potential generation and timing. Neuron 61, 259–271. 10.1016/j.neuron.2008.12.004 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Benfenati V., Nicchia G. P., Svelto M., Rapisarda C., Frigeri A., Ferroni S. (2007). Functional down-regulation of volume-regulated anion channels in AQP4 knockdown cultured rat cortical astrocytes. J. Neurochem. 100, 87–104. 10.1111/j.1471-4159.2006.04164.x [Abstract] [CrossRef] [Google Scholar]
Berkefeld H., Sailer C. A., Bildl W., Rohde V., Thumfart J. O., Eble S., et al. . (2006). BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling. Science 314, 615–620. 10.1126/science.1132915 [Abstract] [CrossRef] [Google Scholar]
Berret E., Barron T., Xu J., Debner E., Kim E. J., Kim J. H. (2017). Oligodendroglial excitability mediated by glutamatergic inputs and Nav1.2 activation. Nat. Commun. 8:557. 10.1038/s41467-017-00688-0 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bhat S., Dao D. T., Terrillion C. E., Arad M., Smith R. J., Soldatov N. M., et al. . (2012). CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease. Prog. Neurobiol. 99, 1–14. 10.1016/j.pneurobio.2012.06.001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bhattacharjee A., Gan L., Kaczmarek L. K. (2002). Localization of the Slack potassium channel in the rat central nervous system. J. Comp. Neurol. 454, 241–254. 10.1002/cne.10439 [Abstract] [CrossRef] [Google Scholar]
Bhattacharjee A., Kaczmarek L. K. (2005). For K+ channels, Na+ is the new Ca2+. Trends Neurosci. 28, 422–428. 10.1016/j.tins.2005.06.003 [Abstract] [CrossRef] [Google Scholar]
Bierbower S. M., Choveau F. S., Lechleiter J. D., Shapiro M. S. (2015). Augmentation of M-type (KCNQ) potassium channels as a novel strategy to reduce stroke-induced brain injury. J. Neurosci. 35, 2101–2111. 10.1523/JNEUROSCI.3805-14.2015 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Birnbaum S. G., Varga A. W., Yuan L. L., Anderson A. E., Sweatt J. D., Schrader L. A. (2004). Structure and function of Kv4-family transient potassium channels. Physiol. Rev. 84, 803–833. 10.1152/physrev.00039.2003 [Abstract] [CrossRef] [Google Scholar]
Bittner S., Ruck T., Fernandez-Orth J., Meuth S. G. (2014). TREK-king the blood-brain-barrier. J. Neuroimmune Pharmacol. 9, 293–301. 10.1007/s11481-014-9530-8 [Abstract] [CrossRef] [Google Scholar]
Bittner S., Ruck T., Schuhmann M. K., Herrmann A. M., Moha ou Maati H., Bobak N., et al. . (2013). Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat. Med. 19, 1161–1165. 10.1038/nm.3303 [Abstract] [CrossRef] [Google Scholar]
Black J. A., Liu S., Waxman S. G. (2009). Sodium channel activity modulates multiple functions in microglia. Glia 57, 1072–1081. 10.1002/glia.20830 [Abstract] [CrossRef] [Google Scholar]
Black J. A., Newcombe J., Trapp B. D., Waxman S. G. (2007). Sodium channel expression within chronic multiple sclerosis plaques. J. Neuropathol. Exp. Neurol. 66, 828–837. 10.1097/nen.0b013e3181462841 [Abstract] [CrossRef] [Google Scholar]
Black J. A., Newcombe J., Waxman S. G. (2010). Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5. Brain 133 (Pt. 3), 835–846. 10.1093/brain/awq003 [Abstract] [CrossRef] [Google Scholar]
Black J. A., Vasylyev D., Dib-Hajj S. D., Waxman S. G. (2014). Nav1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus. Exp. Neurol. 253, 174–179. 10.1016/j.expneurol.2014.01.004 [Abstract] [CrossRef] [Google Scholar]
Black J. A., Waxman S. G. (2012). Sodium channels and microglial function. Exp. Neurol. 234, 302–315. 10.1016/j.expneurol.2011.09.030 [Abstract] [CrossRef] [Google Scholar]
Black J. A., Waxman S. G. (2013). Noncanonical roles of voltage-gated sodium channels. Neuron 80, 280–291. 10.1016/j.neuron.2013.09.012 [Abstract] [CrossRef] [Google Scholar]
Black J. A., Westenbroek R., Minturn J. E., Ransom B. R., Catterall W. A., Waxman S. G. (1995). Isoform-specific expression of sodium channels in astrocytes in vitro: immunocytochemical observations. Glia 14, 133–144. 10.1002/glia.440140208 [Abstract] [CrossRef] [Google Scholar]
Blanz J., Schweizer M., Auberson M., Maier H., Muenscher A., Hubner C. A., et al. . (2007). Leukoencephalopathy upon disruption of the chloride channel ClC-2. J. Neurosci. 27, 6581–6589. 10.1523/JNEUROSCI.0338-07.2007 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Blondeau N., Petrault O., Manta S., Giordanengo V., Gounon P., Bordet R., et al. . (2007). Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel. Circ. Res. 101, 176–184. 10.1161/CIRCRESAHA.107.154443 [Abstract] [CrossRef] [Google Scholar]
Bloodgood B. L., Sabatini B. L. (2008). Regulation of synaptic signalling by postsynaptic, non-glutamate receptor ion channels. J. Physiol. 586, 1475–1480. 10.1113/jphysiol.2007.148353 [Abstract] [CrossRef] [Google Scholar]
Blum R., Kafitz K. W., Konnerth A. (2002). Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9. Nature 419, 687–693. 10.1038/nature01085 [Abstract] [CrossRef] [Google Scholar]
Bock T., Honnuraiah S., Stuart G. J. (2019). Paradoxical excitatory impact of SK channels on dendritic excitability. J. Neurosci. 39, 7826–7839. 10.1523/JNEUROSCI.0105-19.2019 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bocksteins E. (2016). Kv5, Kv6, Kv8, and Kv9 subunits: no simple silent bystanders. J. Gen. Physiol. 147, 105–125. 10.1085/jgp.201511507 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Boiko T., Rasband M. N., Levinson S. R., Caldwell J. H., Mandel G., Trimmer J. S., et al. . (2001). Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron 30, 91–104. 10.1016/s0896-6273(01)00265-3 [Abstract] [CrossRef] [Google Scholar]
Boiko T., Van Wart A., Caldwell J. H., Levinson S. R., Trimmer J. S., Matthews G. (2003). Functional specialization of the axon initial segment by isoform-specific sodium channel targeting. J. Neurosci. 23, 2306–2313. 10.1523/JNEUROSCI.23-06-02306.2003 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Borlot F., Abushama A., Morrison-Levy N., Jain P., Puthenveettil Vinayan K., Abukhalid M., et al. . (2020). KCNT1-related epilepsy: an international multicenter cohort of 27 pediatric cases. Epilepsia 61, 679–692. 10.1111/epi.16480 [Abstract] [CrossRef] [Google Scholar]
Boscia F., Annunziato L., Taglialatela M. (2006). Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures. Neuropharmacology 51, 283–294. 10.1016/j.neuropharm.2006.03.024 [Abstract] [CrossRef] [Google Scholar]
Boscia F., de Rosa V., Cammarota M., Secondo A., Pannaccione A., Annunziato L. (2020). The Na(+)/Ca(2+) exchangers in demyelinating diseases. Cell Calcium 85:102130. 10.1016/j.ceca.2019.102130 [Abstract] [CrossRef] [Google Scholar]
Boscia F., Pannaccione A., Ciccone R., Casamassa A., Franco C., Piccialli I., et al. . (2017). The expression and activity of KV3.4 channel subunits are precociously upregulated in astrocytes exposed to abeta oligomers and in astrocytes of Alzheimer's disease Tg2576 mice. Neurobiol. Aging 54, 187–198. 10.1016/j.neurobiolaging.2017.03.008 [Abstract] [CrossRef] [Google Scholar]
Bose S., He H., Stauber T. (2021). Neurodegeneration upon dysfunction of endosomal/lysosomal CLC chloride transporters. Front. Cell Dev. Biol. 9:639231. 10.3389/fcell.2021.639231 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bouafia A., Golmard J. L., Thuries V., Sazdovitch V., Hauw J. J., Fontaine B., et al. . (2014). Axonal expression of sodium channels and neuropathology of the plaques in multiple sclerosis. Neuropathol. Appl. Neurobiol. 40, 579–590. 10.1111/nan.12059 [Abstract] [CrossRef] [Google Scholar]
Bozarth X., Dines J. N., Cong Q., Mirzaa G. M., Foss K., Lawrence Merritt J. 2nd, et al. . (2018). Expanding clinical phenotype in CACNA1C related disorders: From neonatal onset severe epileptic encephalopathy to late-onset epilepsy. Am. J. Med. Genet. A 176, 2733–2739. 10.1002/ajmg.a.40657 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bradl M., Lassmann H. (2010). Oligodendrocytes: biology and pathology. Acta Neuropathol. 119, 37–53. 10.1007/s00401-009-0601-5 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Brand-Schieber E., Werner P. (2004). Calcium channel blockers ameliorate disease in a mouse model of multiple sclerosis. Exp. Neurol. 189, 5–9. 10.1016/j.expneurol.2004.05.023 [Abstract] [CrossRef] [Google Scholar]
Brasko C., Hawkins V., De La Rocha I. C., Butt A. M. (2017). Expression of Kir4.1 and Kir5.1 inwardly rectifying potassium channels in oligodendrocytes, the myelinating cells of the CNS. Brain Struct. Funct. 222, 41–59. 10.1007/s00429-016-1199-8 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Brill A. L., Fischer T. T., Walters J. M., Marlier A., Sewanan L. R., Wilson P. C., et al. . (2020). Polycystin 2 is increased in disease to protect against stress-induced cell death. Sci. Rep. 10:386. 10.1038/s41598-019-57286-x [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Brown M. R., Kronengold J., Gazula V. R., Spilianakis C. G., Flavell R. A., von Hehn C. A., et al. . (2008). Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation. J. Physiol. 586, 5161–5179. 10.1113/jphysiol.2008.160861 [Abstract] [CrossRef] [Google Scholar]
Brueggemann L. I., Mackie A. R., Cribbs L. L., Freda J., Tripathi A., Majetschak M., et al. . (2014). Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels. J. Biol. Chem. 289, 2099–2111. 10.1074/jbc.M113.527820 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Bruzzone R., Hormuzdi S. G., Barbe M. T., Herb A., Monyer H. (2003). Pannexins, a family of gap junction proteins expressed in brain. Proc. Natl. Acad. Sci. U.S.A. 100, 13644–13649. 10.1073/pnas.2233464100 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cabranes A., Venderova K., de Lago E., Fezza F., Sanchez A., Mestre L., et al. . (2005). Decreased endocannabinoid levels in the brain and beneficial effects of agents activating cannabinoid and/or vanilloid receptors in a rat model of multiple sclerosis. Neurobiol. Dis. 20, 207–217. 10.1016/j.nbd.2005.03.002 [Abstract] [CrossRef] [Google Scholar]
Caldwell J. H., Schaller K. L., Lasher R. S., Peles E., Levinson S. R. (2000). Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc. Natl. Acad. Sci. U.S.A. 97, 5616–5620. 10.1073/pnas.090034797 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Caminos E., Vaquero C. F., Martinez-Galan J. R. (2015). Relationship between rat retinal degeneration and potassium channel KCNQ5 expression. Exp. Eye Res. 131, 1–11. 10.1016/j.exer.2014.12.009 [Abstract] [CrossRef] [Google Scholar]
Casamassa A., La Rocca C., Sokolow S., Herchuelz A., Matarese G., Annunziato L., et al. . (2016). Ncx3 gene ablation impairs oligodendrocyte precursor response and increases susceptibility to experimental autoimmune encephalomyelitis. Glia 64, 1124–1137. 10.1002/glia.22985 [Abstract] [CrossRef] [Google Scholar]
Castellano A., Chiara M. D., Mellstrom B., Molina A., Monje F., Naranjo J. R., et al. . (1997). Identification and functional characterization of a K+ channel alpha-subunit with regulatory properties specific to brain. J. Neurosci. 17, 4652–4661. [Europe PMC free article] [Abstract] [Google Scholar]
Catterall W. A. (2000). Structure and regulation of voltage-gated Ca2+ channels. Annu. Rev. Cell. Dev. Biol. 16, 521–555. 10.1146/annurev.cellbio.16.1.521 [Abstract] [CrossRef] [Google Scholar]
Catterall W. A. (2011). Voltage-gated calcium channels. Cold Spring Harb. Perspect. Biol. 3:a003947. 10.1101/cshperspect.a003947 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cheah C. S., Westenbroek R. E., Roden W. H., Kalume F., Oakley J. C., Jansen L. A., et al. . (2013). Correlations in timing of sodium channel expression, epilepsy, and sudden death in dravet syndrome. Channels 7, 468–472. 10.4161/chan.26023 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Chekeni F. B., Elliott M. R., Sandilos J. K., Walk S. F., Kinchen J. M., Lazarowski E. R., et al. . (2010). Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature 467, 863–867. 10.1038/nature09413 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cheli V. T., Santiago Gonzalez D. A., Namgyal Lama T., Spreuer V., Handley V., Murphy G. G., et al. . (2016a). Conditional deletion of the l-type calcium channel Cav1.2 in oligodendrocyte progenitor cells affects postnatal myelination in mice. J. Neurosci. 36, 10853–10869. 10.1523/JNEUROSCI.1770-16.2016 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cheli V. T., Santiago Gonzalez D. A., Smith J., Spreuer V., Murphy G. G., Paez P. M. (2016b). L-type voltage-operated calcium channels contribute to astrocyte activation in vitro. Glia 64, 1396–1415. 10.1002/glia.23013 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cheli V. T., Santiago Gonzalez D. A., Spreuer V., Paez P. M. (2015). Voltage-gated Ca2+ entry promotes oligodendrocyte progenitor cell maturation and myelination in vitro. Exp. Neurol. 265, 69–83. 10.1016/j.expneurol.2014.12.012 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Chen S., Ren Y. Q., Bing R., Hillman D. E. (2000). Alpha 1E subunit of the R-type calcium channel is associated with myelinogenesis. J. Neurocytol. 29, 719–728. 10.1023/a:1010986303924 [Abstract] [CrossRef] [Google Scholar]
Chen W., Chi Y. N., Kang X. J., Liu Q. Y., Zhang H. L., Li Z. H., et al. . (2018). Accumulation of Cav3.2 T-type calcium channels in the uninjured sural nerve contributes to neuropathic pain in rats with spared nerve injury. Front. Mol. Neurosci. 11:24. 10.3389/fnmol.2018.00024 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Chen Y. L., Tsaur M. L., Wang S. W., Wang T. Y., Hung Y. C., Lin C. S., et al. . (2015). Chronic intrathecal infusion of mibefradil, ethosuximide and nickel attenuates nerve ligation-induced pain in rats. Br. J. Anaesth. 115, 105–111. 10.1093/bja/aev198 [Abstract] [CrossRef] [Google Scholar]
Chittajallu R., Chen Y., Wang H., Yuan X., Ghiani C. A., Heckman T., et al. . (2002). Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc. Natl. Acad. Sci. U.S.A. 99, 2350–2355. 10.1073/pnas.042698399 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Chiu Y. H., Schappe M. S., Desai B. N., Bayliss D. A. (2018). Revisiting multimodal activation and channel properties of pannexin 1. J. Gen. Physiol. 150, 19–39. 10.1085/jgp.201711888 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Choi H. J., Sun D., Jakobs T. C. (2015). Astrocytes in the optic nerve head express putative mechanosensitive channels. Mol. Vis. 21, 749–766. [Europe PMC free article] [Abstract] [Google Scholar]
Christie S., Wittert G. A., Li H., Page A. J. (2018). Involvement of TRPV1 Channels in energy homeostasis. Front. Endocrinol. 9:420. 10.3389/fendo.2018.00420 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Chu S., Murray C. B., Liu M. M., Zeitlin P. L. (1996). A short CIC-2 mRNA transcript is produced by exon skipping. Nucleic Acids Res. 24, 3453–3457. 10.1093/nar/24.17.3453 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Chung K. K., Freestone P. S., Lipski J. (2011). Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the rat. J. Neurophysiol 106, 2865–2875. 10.1152/jn.00994.2010 [Abstract] [CrossRef] [Google Scholar]
Clapham D. E. (2003). TRP channels as cellular sensors. Nature 426, 517–524. 10.1038/nature02196 [Abstract] [CrossRef] [Google Scholar]
Clark S., Jordt S. E., Jentsch T. J., Mathie A. (1998). Characterization of the hyperpolarization-activated chloride current in dissociated rat sympathetic neurons. J. Physiol. 506 (Pt. 3), 665–678. 10.1111/j.1469-7793.1998.665bv.x [Abstract] [CrossRef] [Google Scholar]
Coman I., Aigrot M. S., Seilhean D., Reynolds R., Girault J. A., Zalc B., et al. . (2006). Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis. Brain 129 (Pt. 12), 3186–3195. 10.1093/brain/awl144 [Abstract] [CrossRef] [Google Scholar]
Compston A., Coles A. (2008). Multiple sclerosis. Lancet 372, 1502–1517. 10.1016/S0140-6736(08)61620-7 [Abstract] [CrossRef] [Google Scholar]
Cone A. C., Ambrosi C., Scemes E., Martone M. E., Sosinsky G. E. (2013). A comparative antibody analysis of pannexin1 expression in four rat brain regions reveals varying subcellular localizations. Front. Pharmacol. 4:6. 10.3389/fphar.2013.00006 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cooper E. C. (2011). Made for “anchorin”: Kv7.2/7.3 (KCNQ2/KCNQ3) channels and the modulation of neuronal excitability in vertebrate axons. Semin. Cell Dev. Biol. 22, 185–192. 10.1016/j.semcdb.2010.10.001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cooper E. C., Aldape K. D., Abosch A., Barbaro N. M., Berger M. S., Peacock W. S., et al. . (2000). Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc. Natl. Acad. Sci. U.S.A. 97, 4914–4919. 10.1073/pnas.090092797 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Couturier N., Gourraud P. A., Cournu-Rebeix I., Gout C., Bucciarelli F., Edan G., et al. . (2009). IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients. Eur. J. Hum. Genet. 17, 844–847. 10.1038/ejhg.2008.259 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Craner M. J., Damarjian T. G., Liu S., Hains B. C., Lo A. C., Black J. A., et al. . (2005). Sodium channels contribute to microglia/macrophage activation and function in EAE and MS. Glia 49, 220–229. 10.1002/glia.20112 [Abstract] [CrossRef] [Google Scholar]
Craner M. J., Hains B. C., Lo A. C., Black J. A., Waxman S. G. (2004a). Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain 127 (Pt. 2), 294–303. 10.1093/brain/awh032 [Abstract] [CrossRef] [Google Scholar]
Craner M. J., Lo A. C., Black J. A., Waxman S. G. (2003). Abnormal sodium channel distribution in optic nerve axons in a model of inflammatory demyelination. Brain 126 (Pt. 7), 1552–1561. 10.1093/brain/awg153 [Abstract] [CrossRef] [Google Scholar]
Craner M. J., Newcombe J., Black J. A., Hartle C., Cuzner M. L., Waxman S. G. (2004b). Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger. Proc. Natl. Acad. Sci. U.S.A. 101, 8168–8173. 10.1073/pnas.0402765101 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Crespo Yanguas S., Willebrords J., Johnstone S. R., Maes M., Decrock E., De Bock M., et al. . (2017). Pannexin1 as mediator of inflammation and cell death. Biochim. Biophys. Acta Mol. Cell Res. 1864, 51–61. 10.1016/j.bbamcr.2016.10.006 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Cummins T. R., Dib-Hajj S. D., Black J. A., Akopian A. N., Wood J. N., Waxman S. G. (1999). A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons. J. Neurosci. 19:RC43. [Europe PMC free article] [Abstract] [Google Scholar]
Dahl G. (2015). ATP release through pannexon channels. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370:20140191. 10.1098/rstb.2014.0191 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Dahl G. (2018). The Pannexin1 membrane channel: distinct conformations and functions. FEBS Lett. 592, 3201–3209. 10.1002/1873-3468.13115 [Abstract] [CrossRef] [Google Scholar]
D'Ascenzo M., Vairano M., Andreassi C., Navarra P., Azzena G. B., Grassi C. (2004). Electrophysiological and molecular evidence of L-(Cav1), N- (Cav2.2), and R- (Cav2.3) type Ca2+ channels in rat cortical astrocytes. Glia 45, 354–363. 10.1002/glia.10336 [Abstract] [CrossRef] [Google Scholar]
Daschil N., Geisler S., Obermair G. J., Humpel C. (2014). Short- and long-term treatment of mouse cortical primary astrocytes with beta-amyloid differentially regulates the mRNA expression of L-type calcium channels. Pharmacology 93, 24–31. 10.1159/000357383 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Daschil N., Obermair G. J., Flucher B. E., Stefanova N., Hutter-Paier B., Windisch M., et al. . (2013). CaV1.2 calcium channel expression in reactive astrocytes is associated with the formation of amyloid-beta plaques in an Alzheimer's disease mouse model. J Alzheimers Dis. 37, 439–451. 10.3233/JAD-130560 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
de Kovel C. G. F., Syrbe S., Brilstra E. H., Verbeek N., Kerr B., Dubbs H., et al. . (2017). Neurodevelopmental disorders caused by de novo variants in KCNB1 genotypes and phenotypes. JAMA Neurol. 74, 1228–1236. 10.1001/jamaneurol.2017.1714 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
de Rosa V., Secondo A., Pannaccione A., Ciccone R., Formisano L., Guida N., et al. . (2019). D-Aspartate treatment attenuates myelin damage and stimulates myelin repair. EMBO Mol. Med. 11:e9278. 10.15252/emmm.201809278 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Derbenev A. V., Zsombok A. (2016). Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity. Semin. Immunopathol. 38, 397–406. 10.1007/s00281-015-0529-x [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Derst C., Karschin C., Wischmeyer E., Hirsch J. R., Preisig-Muller R., Rajan S., et al. . (2001). Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits. FEBS Lett. 491, 305–311. 10.1016/s0014-5793(01)02202-5 [Abstract] [CrossRef] [Google Scholar]
Deutsch E., Weigel A. V., Akin E. J., Fox P., Hansen G., Haberkorn C. J., et al. . (2012). Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane. Mol. Biol. Cell 23, 2917–2929. 10.1091/mbc.E12-01-0047 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Devaux J. J., Kleopa K. A., Cooper E. C., Scherer S. S. (2004). KCNQ2 is a nodal K+ channel. J. Neurosci. 24, 1236–1244. 10.1523/JNEUROSCI.4512-03.2004 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Dietrich D., Kirschstein T., Kukley M., Pereverzev A., von der Brelie C., Schneider T., et al. . (2003). Functional specialization of presynaptic Cav2.3 Ca2+ channels. Neuron 39, 483–496. 10.1016/s0896-6273(03)00430-6 [Abstract] [CrossRef] [Google Scholar]
Djillani A., Mazella J., Heurteaux C., Borsotto M. (2019). Role of TREK-1 in health and disease, focus on the central nervous system. Front. Pharmacol. 10:379. 10.3389/fphar.2019.00379 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Dolga A. M., Letsche T., Gold M., Doti N., Bacher M., Chiamvimonvat N., et al. . (2012). Activation of KCNN3/SK3/K(Ca)2.3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia. Glia 60, 2050–2064. 10.1002/glia.22419 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Dolga A. M., Terpolilli N., Kepura F., Nijholt I. M., Knaus H. G., D'Orsi B., et al. . (2011). KCa2 channels activation prevents [Ca2+]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia. Cell Death Dis. 2:e147. 10.1038/cddis.2011.30 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Dorr J., Wernecke K. D., Wurfel J., Bellmann-Strobl J., Siffrin V., Sattler M. B., et al. . (2018). Disease modification in multiple sclerosis by flupirtine-results of a randomized placebo controlled phase II trial. Front. Neurol. 9:842. 10.3389/fneur.2018.00842 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Du J., Haak L. L., Phillips-Tansey E., Russell J. T., McBain C. J. (2000). Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K+ channel subunit Kv2.1. J. Physiol. 522 (Pt. 1), 19–31. 10.1111/j.1469-7793.2000.t01-2-00019.xm [Abstract] [CrossRef] [Google Scholar]
Du T., Liang C., Li B., Hertz L., Peng L. (2014). Chronic fluoxetine administration increases expression of the L-channel gene Cav1.2 in astrocytes from the brain of treated mice and in culture and augments K(+)-induced increase in [Ca(2+)]i. Cell Calcium 55, 166–174. 10.1016/j.ceca.2014.01.002 [Abstract] [CrossRef] [Google Scholar]
Ducharme G., Newell E. W., Pinto C., Schlichter L. C. (2007). Small-conductance Cl- channels contribute to volume regulation and phagocytosis in microglia. Eur. J. Neurosci. 26, 2119–2130. 10.1111/j.1460-9568.2007.05802.x [Abstract] [CrossRef] [Google Scholar]
Duflocq A., Le Bras B., Bullier E., Couraud F., Davenne M. (2008). Nav1.1 is predominantly expressed in nodes of ranvier and axon initial segments. Mol. Cell Neurosci. 39, 180–192. 10.1016/j.mcn.2008.06.008 [Abstract] [CrossRef] [Google Scholar]
Dumenieu M., Oule M., Kreutz M. R., Lopez-Rojas J. (2017). The segregated expression of voltage-gated potassium and sodium channels in neuronal membranes: functional implications and regulatory mechanisms. Front. Cell Neurosci. 11:115. 10.3389/fncel.2017.00115 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Eder C. (1998). Ion channels in microglia (brain macrophages). Am. J. Physiol. 275, C327–342. 10.1152/ajpcell.1998.275.2.C327 [Abstract] [CrossRef] [Google Scholar]
Edwards L., Nashmi R., Jones O., Backx P., Ackerley C., Becker L., et al. . (2002). Upregulation of Kv 1.4 protein and gene expression after chronic spinal cord injury. J Comp. Neurol. 443, 154–167. 10.1002/cne.10115 [Abstract] [CrossRef] [Google Scholar]
Ehling P., Cerina M., Budde T., Meuth S. G., Bittner S. (2015). The CNS under pathophysiologic attack–examining the role of K(2)p channels. Pflugers Arch. 467, 959–972. 10.1007/s00424-014-1664-2 [Abstract] [CrossRef] [Google Scholar]
Eisfeld J., Luckhoff A. (2007). Trpm2. Handb. Exp. Pharmacol. 237–252. 10.1007/978-3-540-34891-7_14 [Abstract] [CrossRef] [Google Scholar]
Elkjaer M. L., Frisch T., Reynolds R., Kacprowski T., Burton M., Kruse T. A., et al. . (2019). Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis. Acta Neuropathol. Commun. 7:205. 10.1186/s40478-019-0855-7 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Elliott C., Belachew S., Wolinsky J. S., Hauser S. L., Kappos L., Barkhof F., et al. . (2019). Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis. Brain 142, 2787–2799. 10.1093/brain/awz212 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Emmi A., Wenzel H. J., Schwartzkroin P. A., Taglialatela M., Castaldo P., Bianchi L., et al. . (2000). Do glia have heart? Expression and functional role for ether-a-go-go currents in hippocampal astrocytes. J. Neurosci. 20, 3915–3925. 10.1523/JNEUROSCI.20-10-03915.2000 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Enders M., Heider T., Ludwig A., Kuerten S. (2020). Strategies for neuroprotection in multiple sclerosis and the role of calcium. Int. J. Mol. Sci. 21:1663. 10.3390/ijms21051663 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Enyedi P., Czirjak G. (2010). Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol. Rev. 90, 559–605. 10.1152/physrev.00029.2009 [Abstract] [CrossRef] [Google Scholar]
Eshed-Eisenbach Y., Peles E. (2020). The clustering of voltage-gated sodium channels in various excitable membranes. Dev. Neurobiol. 1–11. 10.1002/dneu.2272 [Abstract] [CrossRef] [Google Scholar]
Espinosa-Parrilla J. F., Martinez-Moreno M., Gasull X., Mahy N., Rodriguez M. J. (2015). The L-type voltage-gated calcium channel modulates microglial pro-inflammatory activity. Mol. Cell Neurosci. 64, 104–115. 10.1016/j.mcn.2014.12.004 [Abstract] [CrossRef] [Google Scholar]
Estacion M., Gasser A., Dib-Hajj S. D., Waxman S. G. (2010). A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons. Exp. Neurol. 224, 362–368. 10.1016/j.expneurol.2010.04.012 [Abstract] [CrossRef] [Google Scholar]
Falcao A. M., van Bruggen D., Marques S., Meijer M., Jakel S., Agirre E., et al. . (2018). Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis. Nat. Med. 24, 1837–1844. 10.1038/s41591-018-0236-y [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Fang J. S., Angelov S. N., Simon A. M., Burt J. M. (2011). Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery. Am. J. Physiol. Heart Circ. Physiol. 301, H1872–1881. 10.1152/ajpheart.00683.2011 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Fano S., Caliskan G., Heinemann U. (2012). Differential effects of blockade of ERG channels on gamma oscillations and excitability in rat hippocampal slices. Eur. J. Neurosci. 36, 3628–3635. 10.1111/ejn.12015 [Abstract] [CrossRef] [Google Scholar]
Filippi M., Bar-Or A., Piehl F., Preziosa P., Solari A., Vukusic S.. (2018). Multiple sclerosis. Nat. Rev. Dis. Primers 4:43. 10.1038/s41572-018-0041-4 [Abstract] [CrossRef] [Google Scholar]
Fill M., Copello J. A. (2002). Ryanodine receptor calcium release channels. Physiol. Rev. 82, 893–922. 10.1152/physrev.00013.2002 [Abstract] [CrossRef] [Google Scholar]
Foldy C., Lee S. H., Morgan R. J., Soltesz I. (2010). Regulation of fast-spiking basket cell synapses by the chloride channel ClC-2. Nat. Neurosci. 13, 1047–1049. 10.1038/nn.2609 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Fordyce C. B., Jagasia R., Zhu X., Schlichter L. C. (2005). Microglia Kv1.3 channels contribute to their ability to kill neurons. J. Neurosci. 25, 7139–7149. 10.1523/JNEUROSCI.1251-05.2005 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Franceschetti S., Lavazza T., Curia G., Aracri P., Panzica F., Sancini G., et al. . (2003). Na+-activated K+ current contributes to postexcitatory hyperpolarization in neocortical intrinsically bursting neurons. J. Neurophysiol. 89, 2101–2111. 10.1152/jn.00695.2002 [Abstract] [CrossRef] [Google Scholar]
Freestone P. S., Chung K. K., Guatteo E., Mercuri N. B., Nicholson L. F., Lipski J. (2009). Acute action of rotenone on nigral dopaminergic neurons–involvement of reactive oxygen species and disruption of Ca2+ homeostasis. Eur. J. Neurosci. 30, 1849–1859. 10.1111/j.1460-9568.2009.06990.x [Abstract] [CrossRef] [Google Scholar]
Friese M. A., Schattling B., Fugger L. (2014). Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis. Nat. Rev. Neurol. 10, 225–238. 10.1038/nrneurol.2014.37 [Abstract] [CrossRef] [Google Scholar]
Frisch T., Elkjaer M. L., Reynolds R., Michel T. M., Kacprowski T., Burton M., et al. . (2020). Multiple sclerosis atlas: a molecular map of brain lesion stages in progressive multiple sclerosis. Netw. Syst. Med. 3, 122–129. 10.1089/nsm.2020.0006 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Fulton D., Paez P. M., Fisher R., Handley V., Colwell C. S., Campagnoni A. T. (2010). Regulation of L-type Ca++ currents and process morphology in white matter oligodendrocyte precursor cells by golli-myelin proteins. Glia 58, 1292–1303. 10.1002/glia.21008 [Abstract] [CrossRef] [Google Scholar]
Gajardo-Gomez R., Labra V. C., Orellana J. A. (2016). Connexins and pannexins: new insights into microglial functions and dysfunctions. Front. Mol. Neurosci. 9:86. 10.3389/fnmol.2016.00086 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Gallego-Delgado P., James R., Browne E., Meng J., Umashankar S., Tan L., et al. . (2020). Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier. PLoS Biol. 18:e3001008. 10.1371/journal.pbio.3001008 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Gamelli A. E., McKinney B. C., White J. A., Murphy G. G. (2011). Deletion of the L-type calcium channel Ca(V) 1.3 but not Ca(V) 1.2 results in a diminished sAHP in mouse CA1 pyramidal neurons. Hippocampus 21, 133–141. 10.1002/hipo.20728 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Gartner C., Ziegelhoffer B., Kostelka M., Stepan H., Mohr F. W., Dhein S. (2012). Knock-down of endothelial connexins impairs angiogenesis. Pharmacol. Res. 65, 347–357. 10.1016/j.phrs.2011.11.012 [Abstract] [CrossRef] [Google Scholar]
Gasparini S., Kasyanov A. M., Pietrobon D., Voronin L. L., Cherubini E. (2001). Presynaptic R-type calcium channels contribute to fast excitatory synaptic transmission in the rat hippocampus. J. Neurosci. 21, 8715–8721. 10.1523/JNEUROSCI.21-22-08715.2001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Gees M., Colsoul B., Nilius B. (2010). The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb. Perspect. Biol. 2:a003962. 10.1101/cshperspect.a003962 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Giannini G., Conti A., Mammarella S., Scrobogna M., Sorrentino V. (1995). The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. J. CellBiol. 128, 893–904. 10.1083/jcb.128.5.893 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Giaume C., Naus C. C., Saez J. C., Leybaert L. (2021). Glial connexins and pannexins in the healthy and diseased brain. Physiol. Rev. 101, 93–145. 10.1152/physrev.00043.2018 [Abstract] [CrossRef] [Google Scholar]
Gibson H. E., Edwards J. G., Page R. S., Van Hook M. J., Kauer J. A. (2008). TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron 57, 746–759. 10.1016/j.neuron.2007.12.027 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Gilgun-Sherki Y., Panet H., Melamed E., Offen D. (2003). Riluzole suppresses experimental autoimmune encephalomyelitis: implications for the treatment of multiple sclerosis. Brain Res. 989, 196–204. 10.1016/s0006-8993(03)03343-2 [Abstract] [CrossRef] [Google Scholar]
Girolamo F., Coppola C., Ribatti D., Trojano M. (2014). Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol. Commun. 2:84. 10.1186/s40478-014-0084-z [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Gnatenco C., Han J., Snyder A. K., Kim D. (2002). Functional expression of TREK-2 K+ channel in cultured rat brain astrocytes. Brain Res. 931, 56–67. 10.1016/s0006-8993(02)02261-8 [Abstract] [CrossRef] [Google Scholar]
Goldin A. L., Barchi R. L., Caldwell J. H., Hofmann F., Howe J. R., Hunter J. C., et al. . (2000). Nomenclature of voltage-gated sodium channels. Neuron 28, 365–368. 10.1016/s0896-6273(00)00116-1 [Abstract] [CrossRef] [Google Scholar]
Gonzalez-Alvarado M. N., Rotger C., Berger L., London B., Haase S., Kuhbandner K., et al. . (2020). Functional role of endogenous Kv1.4 in experimental demyelination. J. Neuroimmunol. 343:577227. 10.1016/j.jneuroim.2020.577227 [Abstract] [CrossRef] [Google Scholar]
Gonzalez-Reyes L. E., Ladas T. P., Chiang C. C., Durand D. M. (2013). TRPV1 antagonist capsazepine suppresses 4-AP-induced epileptiform activity in vitro and electrographic seizures in vivo. Exp. Neurol. 250, 321–332. 10.1016/j.expneurol.2013.10.010 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Good M. E., Eucker S. A., Li J., Bacon H. M., Lang S. M., Butcher J. T., et al. . (2018). Endothelial cell pannexin1 modulates severity of ischemic stroke by regulating cerebral inflammation and myogenic tone. JCI Insight 3:e96272. 10.1172/jci.insight.96272 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Goppner C., Soria A. H., Hoegg-Beiler M. B., Jentsch T. J. (2020). Cellular basis of ClC-2 Cl- channel-related brain and testis pathologies. J. Biol. Chem. 296:100074. 10.1074/jbc.RA120.016031 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Goswami C., Rademacher N., Smalla K. H., Kalscheuer V., Ropers H. H., Gundelfinger E. D., et al. . (2010). TRPV1 acts as a synaptic protein and regulates vesicle recycling. J. Cell Sci. 123 (Pt. 12), 2045–2057. 10.1242/jcs.065144 [Abstract] [CrossRef] [Google Scholar]
Grunder S., Thiemann A., Pusch M., Jentsch T. J. (1992). Regions involved in the opening of CIC-2 chloride channel by voltage and cell volume. Nature 360, 759–762. 10.1038/360759a0 [Abstract] [CrossRef] [Google Scholar]
Guan D., Tkatch T., Surmeier D. J., Armstrong W. E., Foehring R. C. (2007). Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons. J. Physiol. 581 (Pt. 3), 941–960. 10.1113/jphysiol.2007.128454 [Abstract] [CrossRef] [Google Scholar]
Guo F., Yu N., Cai J. Q., Quinn T., Zong Z. H., Zeng Y. J., et al. . (2008). Voltage-gated sodium channel Nav1.1, Nav1.3 and beta1 subunit were up-regulated in the hippocampus of spontaneously epileptic rat. Brain Res. Bull. 75, 179–187. 10.1016/j.brainresbull.2007.10.005 [Abstract] [CrossRef] [Google Scholar]
Guo L., Schreiber T. H., Weremowicz S., Morton C. C., Lee C., Zhou J. (2000). Identification and characterization of a novel polycystin family member, polycystin-L2, in mouse and human: sequence, expression, alternative splicing, and chromosomal localization. Genomics 64, 241–251. 10.1006/geno.2000.6131 [Abstract] [CrossRef] [Google Scholar]
Gutzmann J. J., Lin L., Hoffman D. A. (2019). Functional coupling of Cav2.3 and BK potassium channels regulates action potential repolarization and short-term plasticity in the mouse hippocampus. Front Cell Neurosci 13, 27. 10.3389/fncel.2019.00027 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Haak L. L., Song L. S., Molinski T. F., Pessah I. N., Cheng H., Russell J. T. (2001). Sparks and puffs in oligodendrocyte progenitors: cross talk between ryanodine receptors and inositol trisphosphate receptors. J. Neurosci. 21, 3860–3870. 10.1523/JNEUROSCI.21-11-03860.2001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Haberlandt C., Derouiche A., Wyczynski A., Haseleu J., Pohle J., Karram K., et al. . (2011). Gray matter NG2 cells display multiple Ca2+-signaling pathways and highly motile processes. PLoS ONE 6:e17575. 10.1371/journal.pone.0017575 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hainz N., Wolf S., Beck A., Wagenpfeil S., Tschernig T., Meier C. (2017). Probenecid arrests the progression of pronounced clinical symptoms in a mouse model of multiple sclerosis. Sci. Rep. 7:17214. 10.1038/s41598-017-17517-5 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hamada M. S., Kole M. H. (2015). Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability. J. Neurosci. 35, 7272–7286. 10.1523/JNEUROSCI.4747-14.2015 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hammann J., Bassetti D., White R., Luhmann H. J., Kirischuk S. (2018). alpha2 isoform of Na(+),K(+)-ATPase via Na(+),Ca(2+) exchanger modulates myelin basic protein synthesis in oligodendrocyte lineage cells in vitro. Cell Calcium 73, 1–10. 10.1016/j.ceca.2018.03.003 [Abstract] [CrossRef] [Google Scholar]
Hammond T. R., Dufort C., Dissing-Olesen L., Giera S., Young A., Wysoker A., et al. . (2019). Single-Cell rna sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50, 253–271.e256. 10.1016/j.immuni.2018.11.004 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hashitani H., Mitsui R. (2019). Role of pericytes in the initiation and propagation of spontaneous activity in the microvasculature. Adv. Exp. Med. Biol. 1124, 329–356. 10.1007/978-981-13-5895-1_14 [Abstract] [CrossRef] [Google Scholar]
Hassan S., Eldeeb K., Millns P. J., Bennett A. J., Alexander S. P., Kendall D. A. (2014). Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br. J. Pharmacol. 171, 2426–2439. 10.1111/bph.12615 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hassen G. W., Feliberti J., Kesner L., Stracher A., Mokhtarian F. (2008). Prevention of axonal injury using calpain inhibitor in chronic progressive experimental autoimmune encephalomyelitis. Brain Res. 1236, 206–215. 10.1016/j.brainres.2008.07.124 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hell J. W., Westenbroek R. E., Warner C., Ahlijanian M. K., Prystay W., Gilbert M. M., et al. . (1993). Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J. Cell Biol. 123, 949–962. 10.1083/jcb.123.4.949 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Herrero-Herranz E., Pardo L. A., Bunt G., Gold R., Stuhmer W., Linker R. A. (2007). Re-expression of a developmentally restricted potassium channel in autoimmune demyelination: Kv1.4 is implicated in oligodendroglial proliferation. Am. J. Pathol. 171, 589–598. 10.2353/ajpath.2007.061241 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Herrero-Herranz E., Pardo L. A., Gold R., Linker R. A. (2008). Pattern of axonal injury in murine myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis: implications for multiple sclerosis. Neurobiol. Dis. 30, 162–173. 10.1016/j.nbd.2008.01.001 [Abstract] [CrossRef] [Google Scholar]
Hervieu G. J., Cluderay J. E., Gray C. W., Green P. J., Ranson J. L., Randall A. D., et al. . (2001). Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS. Neuroscience 103, 899–919. 10.1016/s0306-4522(01)00030-6 [Abstract] [CrossRef] [Google Scholar]
Hibino H., Inanobe A., Furutani K., Murakami S., Findlay I., Kurachi Y. (2010). Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev. 90, 291–366. 10.1152/physrev.00021.2009 [Abstract] [CrossRef] [Google Scholar]
Hirtz J. J., Braun N., Griesemer D., Hannes C., Janz K., Lohrke S., et al. . (2012). Synaptic refinement of an inhibitory topographic map in the auditory brainstem requires functional Cav1.3 calcium channels. J. Neurosci. 32, 14602–14616. 10.1523/JNEUROSCI.0765-12.2012 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Ho K. W., Lambert W. S., Calkins D. J. (2014). Activation of the TRPV1 cation channel contributes to stress-induced astrocyte migration. Glia 62, 1435–1451. 10.1002/glia.22691 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hoegg-Beiler M. B., Sirisi S., Orozco I. J., Ferrer I., Hohensee S., Auberson M., et al. . (2014). Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction. Nat. Commun. 5:3475. 10.1038/ncomms4475 [Abstract] [CrossRef] [Google Scholar]
Hoenderop J. G., Voets T., Hoefs S., Weidema F., Prenen J., Nilius B., et al. . (2003). Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6. EMBO J. 22, 776–785. 10.1093/emboj/cdg080 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hofmann F., Flockerzi V., Kahl S., Wegener J. W. (2014). L-type CaV1.2 calcium channels: from in vitro findings to in vivo function. Physiol. Rev. 94, 303–326. 10.1152/physrev.00016.2013 [Abstract] [CrossRef] [Google Scholar]
Honore E. (2007). The neuronal background K2P channels: focus on TREK1. Nat. Rev. Neurosci. 8, 251–261. 10.1038/nrn2117 [Abstract] [CrossRef] [Google Scholar]
Hoogland T. M., Saggau P. (2004). Facilitation of L-type Ca2+ channels in dendritic spines by activation of beta2 adrenergic receptors. J. Neurosci. 24, 8416–8427. 10.1523/JNEUROSCI.1677-04.2004 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hopp S. C. (2021). Targeting microglia L-type voltage-dependent calcium channels for the treatment of central nervous system disorders. J. Neurosci. Res. 99, 141–162. 10.1002/jnr.24585 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hossain M. M., Sonsalla P. K., Richardson J. R. (2013). Coordinated role of voltage-gated sodium channels and the Na+/H+ exchanger in sustaining microglial activation during inflammation. Toxicol. Appl. Pharmacol. 273, 355–364. 10.1016/j.taap.2013.09.011 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hou X., Zhang R., Wang J., Li Y., Li F., Zhang Y., et al. . (2018). CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation and myelination. Mol. Med. Rep. 17, 4515–4523. 10.3892/mmr.2018.8439 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Howell O. W., Rundle J. L., Garg A., Komada M., Brophy P. J., Reynolds R. (2010). Activated microglia mediate axoglial disruption that contributes to axonal injury in multiple sclerosis. J. Neuropathol. Exp. Neurol. 69, 1017–1033. 10.1097/NEN.0b013e3181f3a5b1 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hu W., Tian C., Li T., Yang M., Hou H., Shu Y. (2009). Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation. Nat. Neurosci. 12, 996–1002. 10.1038/nn.2359 [Abstract] [CrossRef] [Google Scholar]
Huang C. Y., Chu D., Hwang W. C., Tsaur M. L. (2012). Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain. J. Comp. Neurol. 520, 3650–3672. 10.1002/cne.23119 [Abstract] [CrossRef] [Google Scholar]
Huang Y., Fliegert R., Guse A. H., Lu W., Du J. (2020). A structural overview of the ion channels of the TRPM family. Cell Calcium 85:102111. 10.1016/j.ceca.2019.102111 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Hugnot J. P., Salinas M., Lesage F., Guillemare E., de Weille J., Heurteaux C., et al. . (1996). Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards shab and shaw channels. EMBO J. 15, 3322–3331. [Europe PMC free article] [Abstract] [Google Scholar]
Iglesias R., Dahl G., Qiu F., Spray D. C., Scemes E. (2009). Pannexin 1: the molecular substrate of astrocyte “hemichannels”. J. Neurosci. 29, 7092–7097. 10.1523/JNEUROSCI.6062-08.2009 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Iglesias R., Locovei S., Roque A., Alberto A. P., Dahl G., Spray D. C., et al. . (2008). P2X7 receptor-Pannexin1 complex: pharmacology and signaling. Am. J. Physiol. Cell Physiol. 295, C752–760. 10.1152/ajpcell.00228.2008 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Imaizumi T., Kocsis J. D., Waxman S. G. (1999). The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter. Brain Res. 817, 84–92. 10.1016/s0006-8993(98)01214-1 [Abstract] [CrossRef] [Google Scholar]
Indriati D. W., Kamasawa N., Matsui K., Meredith A. L., Watanabe M., Shigemoto R. (2013). Quantitative localization of Cav2.1 (P/Q-type) voltage-dependent calcium channels in Purkinje cells: somatodendritic gradient and distinct somatic coclustering with calcium-activated potassium channels. J. Neurosci. 33, 3668–3678. 10.1523/JNEUROSCI.2921-12.2013 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Inglese M., Madelin G., Oesingmann N., Babb J. S., Wu W., Stoeckel B., et al. . (2010). Brain tissue sodium concentration in multiple sclerosis: a sodium imaging study at 3 tesla. Brain 133 (Pt. 3), 847–857. 10.1093/brain/awp334 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Ingwersen J., De Santi L., Wingerath B., Graf J., Koop B., Schneider R., et al. . (2018). Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis. J. Neurochem. 146, 86–98. 10.1111/jnc.14324 [Abstract] [CrossRef] [Google Scholar]
Irie T., Trussell L. O. (2017). Double-Nanodomain coupling of calcium channels, ryanodine receptors, and BK channels controls the generation of burst firing. Neuron 96, 856–870.e854. 10.1016/j.neuron.2017.10.014 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Izquierdo-Serra M., Fernandez-Fernandez J. M., Serrano M. (2020). Rare CACNA1A mutations leading to congenital ataxia. Pflugers Arch. 472, 791–809. 10.1007/s00424-020-02396-z [Abstract] [CrossRef] [Google Scholar]
Jakel S., Agirre E., Mendanha Falcao A., van Bruggen D., Lee K. W., Knuesel I., et al. . (2019). Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature 566, 543–547. 10.1038/s41586-019-0903-2 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Jäkel S., Williams A. (2020). What have advances in transcriptomic technologies taught us about human white matter pathologies? Front. Cell Neurosci. 14:238. 10.3389/fncel.2020.00238 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Jentsch T. J. (2000). Neuronal KCNQ potassium channels: physiology and role in disease. Nat. Rev. Neurosci. 1, 21–30. 10.1038/35036198 [Abstract] [CrossRef] [Google Scholar]
Jentsch T. J., Maritzen T., Zdebik A. A. (2005). Chloride channel diseases resulting from impaired transepithelial transport or vesicular function. J. Clin. Invest. 115, 2039–2046. 10.1172/JCI25470 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Jentsch T. J., Pusch M. (2018). CLC chloride channels and transporters: structure, function, physiology, and disease. Physiol. Rev. 98, 1493–1590. 10.1152/physrev.00047.2017 [Abstract] [CrossRef] [Google Scholar]
Jeong S. Y., Goto J., Hashida H., Suzuki T., Ogata K., Masuda N., et al. . (2000). Identification of a novel human voltage-gated sodium channel alpha subunit gene, SCN12A. Biochem. Biophys. Res. Commun. 267, 262–270. 10.1006/bbrc.1999.1916 [Abstract] [CrossRef] [Google Scholar]
Jeworutzki E., Lopez-Hernandez T., Capdevila-Nortes X., Sirisi S., Bengtsson L., Montolio M., et al. . (2012). GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-) channel auxiliary subunit. Neuron 73, 951–961. 10.1016/j.neuron.2011.12.039 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Jin X., Yu L., Wu Y., Zhang S., Shi Z., Chen X., et al. . (2012). S-Glutathionylation underscores the modulation of the heteromeric Kir4.1-Kir5.1 channel in oxidative stress. J. Physiol. 590, 5335–5348. 10.1113/jphysiol.2012.236885 [Abstract] [CrossRef] [Google Scholar]
Johnson B., Leek A. N., Tamkun M. M. (2019). Kv2 channels create endoplasmic reticulum/plasma membrane junctions: a brief history of Kv2 channel subcellular localization. Channels 13, 88–101. 10.1080/19336950.2019.1568824 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Johnson K. W., Herold K. F., Milner T. A., Hemmings H. C., Jr., Platholi J. (2017). Sodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus. J. Comp. Neurol. 525, 3563–3578. 10.1002/cne.24291 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Jones S. L., Stuart G. J. (2013). Different calcium sources control somatic versus dendritic SK channel activation during action potentials. J. Neurosci. 33, 19396–19405. 10.1523/JNEUROSCI.2073-13.2013 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Joux N., Chevaleyre V., Alonso G., Boissin-Agasse L., Moos F. C., Desarmenien M. G., et al. . (2001). High voltage-activated Ca2+ currents in rat supraoptic neurones: biophysical properties and expression of the various channel alpha1 subunits. J. Neuroendocrinol. 13, 638–649. 10.1046/j.1365-2826.2001.00679.x [Abstract] [CrossRef] [Google Scholar]
Jukkola P., Gu C. (2015). Regulation of neurovascular coupling in autoimmunity to water and ion channels. Autoimmun. Rev. 14, 258–267. 10.1016/j.autrev.2014.11.010 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Jukkola P., Gu Y., Lovett-Racke A. E., Gu C. (2017). Suppression of inflammatory demyelinaton and axon degeneration through inhibiting Kv3 channels. Front. Mol. Neurosci. 10:344. 10.3389/fnmol.2017.00344 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Jukkola P. I., Lovett-Racke A. E., Zamvil S. S., Gu C. (2012). K+ channel alterations in the progression of experimental autoimmune encephalomyelitis. Neurobiol. Dis. 47, 280–293. 10.1016/j.nbd.2012.04.012 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Justice J. A., Schulien A. J., He K., Hartnett K. A., Aizenman E., Shah N. H. (2017). Disruption of KV2.1 somato-dendritic clusters prevents the apoptogenic increase of potassium currents. Neuroscience 354, 158–167. 10.1016/j.neuroscience.2017.04.034 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kamijo S., Ishii Y., Horigane S. I., Suzuki K., Ohkura M., Nakai J., et al. . (2018). A critical neurodevelopmental role for L-type voltage-gated calcium channels in neurite extension and radial migration. J. Neurosci. 38, 5551–5566. 10.1523/JNEUROSCI.2357-17.2018 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kanda H., Ling J., Tonomura S., Noguchi K., Matalon S., Gu J. G. (2019). TREK-1 and TRAAK are principal K(+) channels at the nodes of ranvier for rapid action potential conduction on mammalian myelinated afferent nerves. Neuron 104, 960–971.e967. 10.1016/j.neuron.2019.08.042 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Karim Z., Sawada A., Kawakami H., Yamamoto T., Taniguchi T. (2006). A new calcium channel antagonist, lomerizine, alleviates secondary retinal ganglion cell death after optic nerve injury in the rat. Curr. Eye Res. 31, 273–283. 10.1080/02713680500536647 [Abstract] [CrossRef] [Google Scholar]
Kasper D., Planells-Cases R., Fuhrmann J. C., Scheel O., Zeitz O., Ruether K., et al. . (2005). Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. EMBO J. 24, 1079–1091. 10.1038/sj.emboj.7600576 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kastriti M. E., Sargiannidou I., Kleopa K. A., Karagogeos D. (2015). Differential modulation of the juxtaparanodal complex in multiple sclerosis. Mol. Cell Neurosci. 67, 93–103. 10.1016/j.mcn.2015.06.005 [Abstract] [CrossRef] [Google Scholar]
Kelley K. W., Ben Haim L., Schirmer L., Tyzack G. E., Tolman M., Miller J. G., et al. . (2018). Kir4.1-dependent astrocyte-fast motor neuron interactions are required for peak strength. Neuron 98, 306–319.e307. 10.1016/j.neuron.2018.03.010 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kesherwani V., Agrawal S. K. (2012). Upregulation of RyR2 in hypoxic/reperfusion injury. J. Neurotrauma 29, 1255–1265. 10.1089/neu.2011.1780 [Abstract] [CrossRef] [Google Scholar]
Kharkovets T., Hardelin J. P., Safieddine S., Schweizer M., El-Amraoui A., Petit C., et al. . (2000). KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway. Proc. Natl. Acad. Sci. U.S.A. 97, 4333–4338. 10.1073/pnas.97.8.4333 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kim G. E., Kaczmarek L. K. (2014). Emerging role of the KCNT1 Slack channel in intellectual disability. Front. Cell Neurosci. 8:209. 10.3389/fncel.2014.00209 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kim J. W., Oh H. A., Lee S. H., Kim K. C., Eun P. H., Ko M. J., et al. . (2018). T-Type calcium channels are required to maintain viability of neural progenitor cells. Biomol. Ther. 26, 439–445. 10.4062/biomolther.2017.223 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kim S. R., Kim S. U., Oh U., Jin B. K. (2006). Transient receptor potential vanilloid subtype 1 mediates microglial cell death in vivo and in vitro via Ca2+-mediated mitochondrial damage and cytochrome c release. J. Immunol. 177, 4322–4329. 10.4049/jimmunol.177.7.4322 [Abstract] [CrossRef] [Google Scholar]
Kirmiz M., Palacio S., Thapa P., King A. N., Sack J. T., Trimmer J. S. (2018). Remodeling neuronal ER-PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels. Mol. Biol. Cell 29, 2410–2432. 10.1091/mbc.E18-05-0337 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Kleefuss-Lie A., Friedl W., Cichon S., Haug K., Warnstedt M., Alekov A., et al. . (2009). CLCN2 variants in idiopathic generalized epilepsy. Nat. Genet. 41, 954–955. 10.1038/ng0909-954 [Abstract] [CrossRef] [Google Scholar]
Klegeris A., Choi H. B., McLarnon J. G., McGeer P. L. (2007). Functional ryanodine receptors are expressed by human microglia and THP-1 cells: their possible involvement in modulation of neurotoxicity. J. Neurosci. Res. 85, 2207–2215. 10.1002/jnr.21361 [Abstract] [CrossRef] [Google Scholar]
Kole M. H., Stuart G. J. (2012). Signal processing in the axon initial segment. Neuron 73, 235–247. 10.1016/j.neuron.2012.01.007 [Abstract] [CrossRef] [Google Scholar]
Kong W. L., Peng Y. Y., Peng B. W. (2017). Modulation of neuroinflammation: role and therapeutic potential of TRPV1 in the neuro-immune axis. Brain. Behav. Immun. 64, 354–366. 10.1016/j.bbi.2017.03.007 [Abstract] [CrossRef] [Google Scholar]
Konstas A. A., Korbmacher C., Tucker S. J. (2003). Identification of domains that control the heteromeric assembly of Kir5.1/Kir4.0 potassium channels. Am. J. Physiol. Cell Physiol. 284, C910–917. 10.1152/ajpcell.00479.2002 [Abstract] [CrossRef] [Google Scholar]
Kornak U., Kasper D., Bosl M. R., Kaiser E., Schweizer M., Schulz A., et al. . (2001). Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 104, 205–215. 10.1016/s0092-8674(01)00206-9 [Abstract] [CrossRef] [Google Scholar]
Kuhlmann T., Ludwin S., Prat A., Antel J., Bruck W., Lassmann H. (2017). An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 133, 13–24. 10.1007/s00401-016-1653-y [Abstract] [CrossRef] [Google Scholar]
Kurowski P., Gawlak M., Szulczyk P. (2015). Muscarinic receptor control of pyramidal neuron membrane potential in the medial prefrontal cortex (mPFC) in rats. Neuroscience 303, 474–488. 10.1016/j.neuroscience.2015.07.023 [Abstract] [CrossRef] [Google Scholar]
Kushnir A., Wajsberg B., Marks A. R. (2018). Ryanodine receptor dysfunction in human disorders. Biochim. Biophys. Acta. Mol. Cell Res. 1865 (11 Pt. B), 1687–1697. 10.1016/j.bbamcr.2018.07.011 [Abstract] [CrossRef] [Google Scholar]
Lanner J. T., Georgiou D. K., Joshi A. D., Hamilton S. L. (2010). Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb. Perspect. Biol. 2:a003996. 10.1101/cshperspect.a003996 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Lapato A. S., Tiwari-Woodruff S. K. (2018). Connexins and pannexins: At the junction of neuro-glial homeostasis & disease. J. Neurosci. Res. 96, 31–44. 10.1002/jnr.24088 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Larson V. A., Zhang Y., Bergles D. E. (2016). Electrophysiological properties of NG2(+) cells: Matching physiological studies with gene expression profiles. Brain Res. 1638 (Pt. B):138–160. 10.1016/j.brainres.2015.09.010 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Latour I., Hamid J., Beedle A. M., Zamponi G. W., Macvicar B. A. (2003). Expression of voltage-gated Ca2+ channel subtypes in cultured astrocytes. Glia 41, 347–353. 10.1002/glia.10162 [Abstract] [CrossRef] [Google Scholar]
Lee S. C., Choi S., Lee T., Kim H. L., Chin H., Shin H. S. (2002). Molecular basis of R-type calcium channels in central amygdala neurons of the mouse. Proc. Natl. Accad. Sci. U.S.A. 99, 3276–3281. 10.1073/pnas.052697799 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Lee Y. J., Yum M. S., Kim M. J., Shim W. H., Yoon H. M., Yoo I. H., et al. . (2017). Large-scale structural alteration of brain in epileptic children with SCN1A mutation. Neuroimage Clin. 15, 594–600. 10.1016/j.nicl.2017.06.002 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Leithe E., Mesnil M., Aasen T. (2018). The connexin 43 C-terminus: a tail of many tales. Biochim. Biophys. Acta Biomembr. 1860, 48–64. 10.1016/j.bbamem.2017.05.008 [Abstract] [CrossRef] [Google Scholar]
Li F., Lu J., Wu C. Y., Kaur C., Sivakumar V., Sun J., et al. . (2008). Expression of Kv1.2 in microglia and its putative roles in modulating production of proinflammatory cytokines and reactive oxygen species. J. Neurochem. 106, 2093–2105. 10.1111/j.1471-4159.2008.05559.x [Abstract] [CrossRef] [Google Scholar]
Li L., Li J., Zuo Y., Dang D., Frost J. A., Yang Q. (2019). Activation of KCNQ channels prevents paclitaxel-induced peripheral neuropathy and associated neuropathic pain. J. Pain 20, 528–539. 10.1016/j.jpain.2018.11.001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Li T., Wang L., Ma T., Wang S., Niu J., Li H., et al. . (2018). Dynamic calcium release from endoplasmic reticulum mediated by ryanodine receptor 3 is crucial for oligodendroglial differentiation. Front. Mol. Neurosci. 11:162. 10.3389/fnmol.2018.00162 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Li Y., Tatsui C. E., Rhines L. D., North R. Y., Harrison D. S., Cassidy R. M., et al. . (2017). Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy. Pain 158, 417–429. 10.1097/j.pain.0000000000000774 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Li Z., Zhang S., Cao L., Li W., Ye Y. C., Shi Z. X., et al. . (2018). Tanshinone IIA and Astragaloside IV promote the angiogenesis of mesenchymal stem cell-derived endothelial cell-like cells via upregulation of Cx37, Cx40 and Cx43. Exp. Ther. Med. 15, 1847–1854. 10.3892/etm.2017.5636 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Liao B., Zhang Y., Sun H., Ma B., Qian J. (2016). Ryanodine receptor 2 plays a critical role in spinal cord injury via induction of oxidative stress. Cell Physiol. Biochem. 38, 1129–1137. 10.1159/000443063 [Abstract] [CrossRef] [Google Scholar]
Liao Y. J., Jan Y. N., Jan L. Y. (1996). Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brain. J. Neurosci. 16, 7137–7150. [Europe PMC free article] [Abstract] [Google Scholar]
Lindia J. A., Abbadie C. (2003). Distribution of the voltage gated sodium channel Na(v)1.3-like immunoreactivity in the adult rat central nervous system. Brain Res. 60, 132–141. 10.1016/s0006-8993(02)03802-7 [Abstract] [CrossRef] [Google Scholar]
Lipscombe D., Helton T. D., Xu W. (2004). L-type calcium channels: the low down. J. Neurophysiol. 92, 2633–2641. 10.1152/jn.00486.2004 [Abstract] [CrossRef] [Google Scholar]
Lishko P. V., Mannowetz N. (2018). CatSper: a unique calcium channel of the sperm flagellum. Curr. Opin. Physiol. 2, 109–113. 10.1016/j.cophys.2018.02.004 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Liu X., Hernandez N., Kisselev S., Floratos A., Sawle A., Ionita-Laza I., et al. . (2016). Identification of candidate genes for familial early-onset essential tremor. Eur. J. Hum. Genet. 24, 1009–1015. 10.1038/ejhg.2015.228 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Locovei S., Scemes E., Qiu F., Spray D. C., Dahl G. (2007). Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett. 581, 483–488. 10.1016/j.febslet.2006.12.056 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Lory P., Nicole S., Monteil A. (2020). Neuronal Cav3 channelopathies: recent progress and perspectives. Pflugers Arch. 472, 831–844. 10.1007/s00424-020-02429-7 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Ludwig J., Weseloh R., Karschin C., Liu Q., Netzer R., Engeland B., et al. . (2000). Cloning and functional expression of rat eag2, a new member of the ether-a-go-go family of potassium channels and comparison of its distribution with that of eag1. Mol. Cell Neurosci. 16, 59–70. 10.1006/mcne.2000.0851 [Abstract] [CrossRef] [Google Scholar]
Lugaresi A. (2015). Pharmacology and clinical efficacy of dalfampridine for treating multiple sclerosis. Expert. Opin. Drug Metab. Toxicol. 11, 295–306. 10.1517/17425255.2015.993315 [Abstract] [CrossRef] [Google Scholar]
Luscher C., Slesinger P. A. (2010). Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat. Rev. Neurosci. 11, 301–315. 10.1038/nrn2834 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Lutz S. E., Gonzalez-Fernandez E., Ventura J. C., Perez-Samartin A., Tarassishin L., Negoro H., et al. . (2013). Contribution of pannexin1 to experimental autoimmune encephalomyelitis. PLoS ONE 8:e66657. 10.1371/journal.pone.0066657 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Ma W., Compan V., Zheng W., Martin E., North R. A., Verkhratsky A., et al. . (2012). Pannexin 1 forms an anion-selective channel. Pflugers Arch. 463, 585–592. 10.1007/s00424-012-1077-z [Abstract] [CrossRef] [Google Scholar]
Majumdar A., Capetillo-Zarate E., Cruz D., Gouras G. K., Maxfield F. R. (2011). Degradation of Alzheimer's amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes. Mol. Biol. Cell 22, 1664–1676. 10.1091/mbc.E10-09-0745 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Malko P., Syed Mortadza S. A., McWilliam J., Jiang L. H. (2019). TRPM2 channel in microglia as a new player in neuroinflammation associated with a spectrum of central nervous system pathologies. Front. Pharmacol. 10:239. 10.3389/fphar.2019.00239 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Marques S., Zeisel A., Codeluppi S., van Bruggen D., Mendanha Falcao A., Xiao L., et al. . (2016). Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science 352, 1326–1329. 10.1126/science.aaf6463 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Marrone M. C., Morabito A., Giustizieri M., Chiurchiu V., Leuti A., Mattioli M., et al. . (2017). TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice. Nat. Commun. 8:15292. 10.1038/ncomms15292 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Martin N. A., Nawrocki A., Molnar V., Elkjaer M. L., Thygesen E. K., Palkovits M., et al. . (2018). Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes. PLoS ONE 13:e0202530. 10.1371/journal.pone.0202530 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Martinez A., Santiago J. L., Cenit M. C., de Las Heras V., de la Calle H., Fernandez-Arquero M., et al. . (2008). IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk. Eur. J. Hum. Genet. 16, 861–864. 10.1038/ejhg.2008.16 [Abstract] [CrossRef] [Google Scholar]
Matyash M., Matyash V., Nolte C., Sorrentino V., Kettenmann H. (2002). Requirement of functional ryanodine receptor type 3 for astrocyte migration. FASEB J 16, 84–86. 10.1096/fj.01-0380fje [Abstract] [CrossRef] [Google Scholar]
Mayfield J., Blednov Y. A., Harris R. A. (2015). Behavioral and genetic evidence for girk channels in the cns: role in physiology, pathophysiology, and drug addiction. Int. Rev. Neurobiol. 123, 279–313. 10.1016/bs.irn.2015.05.016 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
McDonald W. I., Sears T. A. (1969). Effect of demyelination on conduction in the central nervous system. Nature. 221, 182–183. 10.1038/221182a0 [Abstract] [CrossRef] [Google Scholar]
McKay B. E., McRory J. E., Molineux M. L., Hamid J., Snutch T. P., Zamponi G. W., et al. . (2006). Ca(V)3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. Eur. J. Neurosci. 24, 2581–2594. 10.1111/j.1460-9568.2006.05136.x [Abstract] [CrossRef] [Google Scholar]
McKinney B. C., Sze W., Lee B., Murphy G. G. (2009). Impaired long-term potentiation and enhanced neuronal excitability in the amygdala of Ca(V)1.3 knockout mice. Neurobiol. Learn. Mem. 92, 519–528. 10.1016/j.nlm.2009.06.012 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
McPherson P. S., Campbell K. P. (1990). Solubilization and biochemical characterization of the high affinity [3H]ryanodine receptor from rabbit brain membranes. J. Biol. Chem. 265, 18454–18460. [Abstract] [Google Scholar]
McTague A., Appleton R., Avula S., Cross J. H., King M. D., Jacques T. S., et al. . (2013). Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum. Brain 136 (Pt. 5), 1578–1591. 10.1093/brain/awt073 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Meisler M. H. (2019). SCN8A encephalopathy: mechanisms and models. Epilepsia 60 (Suppl. 3), S86–S91. 10.1111/epi.14703 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Melzer N., Hicking G., Gobel K., Wiendl H. (2012). TRPM2 cation channels modulate T cell effector functions and contribute to autoimmune CNS inflammation. PLoS ONE 7:e47617. 10.1371/journal.pone.0047617 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Miceli F., Soldovieri M. V., Ambrosino P., Barrese V., Migliore M., Cilio M. R., et al. . (2013). Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of K(v)7.2 potassium channel subunits. Proc. Natl. Acad. Sci. U.S.A. 110, 4386–4391. 10.1073/pnas.1216867110 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Miceli F., Soldovieri M. V., Martire M., Taglialatela M. (2008). Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating drugs. Curr. Opin. Pharmacol. 8, 65–74. 10.1016/j.coph.2007.10.003 [Abstract] [CrossRef] [Google Scholar]
Micu I., Plemel J. R., Lachance C., Proft J., Jansen A. J., Cummins K., et al. . (2016). The molecular physiology of the axo-myelinic synapse. Exp. Neurol. 276, 41–50. 10.1016/j.expneurol.2015.10.006 [Abstract] [CrossRef] [Google Scholar]
Miyake T., Shirakawa H., Nakagawa T., Kaneko S. (2015). Activation of mitochondrial transient receptor potential vanilloid 1 channel contributes to microglial migration. Glia 63, 1870–1882. 10.1002/glia.22854 [Abstract] [CrossRef] [Google Scholar]
Mochida S. (2019). Presynaptic calcium channels. Int. J. Mol. Sci. 20:2217. 10.3390/ijms20092217 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Mori F., Ribolsi M., Kusayanagi H., Monteleone F., Mantovani V., Buttari F., et al. . (2012). TRPV1 channels regulate cortical excitability in humans. J. Neurosci. 32, 873–879. 10.1523/JNEUROSCI.2531-11.2012 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Mulkey D. K., Wenker I. C. (2011). Astrocyte chemoreceptors: mechanisms of H+ sensing by astrocytes in the retrotrapezoid nucleus and their possible contribution to respiratory drive. Exp. Physiol. 96, 400–406. 10.1113/expphysiol.2010.053140 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Musumeci G., Grasselli G., Rossi S., De Chiara V., Musella A., Motta C., et al. . (2011). Transient receptor potential vanilloid 1 channels modulate the synaptic effects of TNF-alpha and of IL-1beta in experimental autoimmune encephalomyelitis. Neurobiol. Dis. 43, 669–677. 10.1016/j.nbd.2011.05.018 [Abstract] [CrossRef] [Google Scholar]
Nagamine K., Kudoh J., Minoshima S., Kawasaki K., Asakawa S., Ito F., et al. . (1998). Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. Genomics 54, 124–131. 10.1006/geno.1998.5551 [Abstract] [CrossRef] [Google Scholar]
Nagy B., Hovhannisyan A., Barzan R., Chen T. J., Kukley M. (2017). Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum. PLoS Biol. 15:e2001993. 10.1371/journal.pbio.2001993 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Namadurai S., Yereddi N. R., Cusdin F. S., Huang C. L., Chirgadze D. Y., Jackson A. P. (2015). A new look at sodium channel beta subunits. Open Biol. 5:140192. 10.1098/rsob.140192 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Naziroglu M., Luckhoff A. (2008). A calcium influx pathway regulated separately by oxidative stress and ADP-Ribose in TRPM2 channels: single channel events. Neurochem. Res. 33, 1256–1262. 10.1007/s11064-007-9577-5 [Abstract] [CrossRef] [Google Scholar]
Nerbonne J. M., Gerber B. R., Norris A., Burkhalter A. (2008). Electrical remodelling maintains firing properties in cortical pyramidal neurons lacking KCND2-encoded A-type K+ currents. J. Physiol. 586, 1565–1579. 10.1113/jphysiol.2007.146597 [Abstract] [CrossRef] [Google Scholar]
Neusch C., Rozengurt N., Jacobs R. E., Lester H. A., Kofuji P. (2001). Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J Neurosci 21, 5429–5438 [Europe PMC free article] [Abstract] [Google Scholar]
Nicoletti N. F., Erig T. C., Zanin R. F., Roxo M. R., Ferreira N. P., Gomez M. V., et al. . (2017). Pre-clinical evaluation of voltage-gated calcium channel blockers derived from the spider P. nigriventer in glioma progression. Toxicon 129, 58–67. 10.1016/j.toxicon.2017.02.001 [Abstract] [CrossRef] [Google Scholar]
Nijenhuis T., Hoenderop J. G., van der Kemp A. W., Bindels R. J. (2003). Localization and regulation of the epithelial Ca2+ channel TRPV6 in the kidney. J. Am. Soc. Nephrol. 14, 2731–2740. 10.1097/01.asn.0000094081.78893.e8 [Abstract] [CrossRef] [Google Scholar]
Nilius B., Owsianik G. (2011). The transient receptor potential family of ion channels. Genome Biol. 12:218. 10.1186/gb-2011-12-3-218 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Niu J., Li T., Yi C., Huang N., Koulakoff A., Weng C., et al. . (2016). Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage. J. Cell Sci. 129, 1902–1914. 10.1242/jcs.178731 [Abstract] [CrossRef] [Google Scholar]
Nodera H., Spieker A., Sung M., Rutkove S. (2011). Neuroprotective effects of Kv7 channel agonist, retigabine, for cisplatin-induced peripheral neuropathy. Neurosci. Lett. 505, 223–227. 10.1016/j.neulet.2011.09.013 [Abstract] [CrossRef] [Google Scholar]
Obermair G. J., Szabo Z., Bourinet E., Flucher B. E. (2004). Differential targeting of the L-type Ca2+ channel alpha 1C (CaV1.2) to synaptic and extrasynaptic compartments in hippocampal neurons. Eur. J. Neurosci. 19, 2109–2122. 10.1111/j.0953-816X.2004.03272.x [Abstract] [CrossRef] [Google Scholar]
O'Brien J. E., Meisler M. H. (2013). Sodium channel SCN8A (Nav1.6): properties and de novo mutations in epileptic encephalopathy and intellectual disability. Front. Genet. 4, 213. 10.3389/fgene.2013.00213 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Ogiwara I., Miyamoto H., Morita N., Atapour N., Mazaki E., Inoue I., et al. . (2007). Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J. Neurosci. 27, 5903–5914. 10.1523/JNEUROSCI.5270-06.2007 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Olah M. E., Jackson M. F., Li H., Perez Y., Sun H. S., Kiyonaka S., et al. . (2009). Ca2+-dependent induction of TRPM2 currents in hippocampal neurons. J. Physiol. 587 (Pt. 5), 965–979. 10.1113/jphysiol.2008.162289 [Abstract] [CrossRef] [Google Scholar]
O'Malley H. A., Shreiner A. B., Chen G. H., Huffnagle G. B., Isom L. L. (2009). Loss of Na+ channel beta2 subunits is neuroprotective in a mouse model of multiple sclerosis. Mol. Cell Neurosci. 40, 143–155. 10.1016/j.mcn.2008.10.001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Orellana J. A., Froger N., Ezan P., Jiang J. X., Bennett M. V., Naus C. C., et al. . (2011). ATP and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels. J. Neurochem. 118, 826–840. 10.1111/j.1471-4159.2011.07210.x [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Orellana J. A., Montero T. D., von Bernhardi R. (2013). Astrocytes inhibit nitric oxide-dependent Ca(2+) dynamics in activated microglia: involvement of ATP released via pannexin 1 channels. Glia 61, 2023–2037. 10.1002/glia.22573 [Abstract] [CrossRef] [Google Scholar]
Orem B. C., Pelisch N., Williams J., Nally J. M., Stirling D. P. (2017). Intracellular calcium release through IP3R or RyR contributes to secondary axonal degeneration. Neurobiol. Dis. 106, 235–243. 10.1016/j.nbd.2017.07.011 [Abstract] [CrossRef] [Google Scholar]
Ortner N. J., Striessnig J. (2016). L-type calcium channels as drug targets in CNS disorders. Channels 10, 7–13. 10.1080/19336950.2015.1048936 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Osorio N., Alcaraz G., Padilla F., Couraud F., Delmas P., Crest M. (2005). Differential targeting and functional specialization of sodium channels in cultured cerebellar granule cells. J. Physiol. 569 (Pt. 3), 801–816. 10.1113/jphysiol.2005.097022 [Abstract] [CrossRef] [Google Scholar]
Ouardouz M., Nikolaeva M. A., Coderre E., Zamponi G. W., McRory J. E., Trapp B. D., et al. . (2003). Depolarization-induced Ca2+ release in ischemic spinal cord white matter involves L-type Ca2+ channel activation of ryanodine receptors. Neuron 40, 53–63. 10.1016/j.neuron.2003.08.016 [Abstract] [CrossRef] [Google Scholar]
Ovsepian S. V., LeBerre M., Steuber V., O'Leary V. B., Leibold C., Oliver Dolly J. (2016). Distinctive role of KV1.1 subunit in the biology and functions of low threshold K(+) channels with implications for neurological disease. Pharmacol. Ther. 159, 93–101. 10.1016/j.pharmthera.2016.01.005 [Abstract] [CrossRef] [Google Scholar]
Paez P. M., Cheli V. T., Ghiani C. A., Spreuer V., Handley V. W., Campagnoni A. T. (2012). Golli myelin basic proteins stimulate oligodendrocyte progenitor cell proliferation and differentiation in remyelinating adult mouse brain. Glia 60, 1078–1093. 10.1002/glia.22336 [Abstract] [CrossRef] [Google Scholar]
Paez P. M., Fulton D., Colwell C. S., Campagnoni A. T. (2009). Voltage-operated Ca(2+) and Na(+) channels in the oligodendrocyte lineage. J. Neurosci. Res. 87, 3259–3266. 10.1002/jnr.21938 [Abstract] [CrossRef] [Google Scholar]
Paez P. M., Lyons D. A. (2020). Calcium signaling in the oligodendrocyte lineage: regulators and consequences. Annu. Rev. Neurosci. 43, 163–186. 10.1146/annurev-neuro-100719-093305 [Abstract] [CrossRef] [Google Scholar]
Paltser G., Liu X. J., Yantha J., Winer S., Tsui H., Wu P., et al. . (2013). TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. Mol. Med. 19, 149–159. 10.2119/molmed.2012.00329 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Pan Z., Kao T., Horvath Z., Lemos J., Sul J. Y., Cranstoun S. D., et al. . (2006). A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J. Neurosci. 26, 2599–2613. 10.1523/JNEUROSCI.4314-05.2006 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Papa M., Boscia F., Canitano A., Castaldo P., Sellitti S., Annunziato L., et al. . (2003). Expression pattern of the ether-a-gogo-related (ERG) K+ channel-encoding genes ERG1, ERG2, and ERG3 in the adult rat central nervous system. J Comp Neurol 466, 119–135. 10.1002/cne.10886 [Abstract] [CrossRef] [Google Scholar]
Papanikolaou M., Butt A. M., Lewis A. (2020). A critical role for the inward rectifying potassium channel Kir7.1 in oligodendrocytes of the mouse optic nerve. Brain Struct. Funct. 225, 925–934. 10.1007/s00429-020-02043-4 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Pappalardo L. W., Black J. A., Waxman S. G. (2016). Sodium channels in astroglia and microglia. Glia 64, 1628–1645. 10.1002/glia.22967 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Parajuli L. K., Nakajima C., Kulik A., Matsui K., Schneider T., Shigemoto R., et al. . (2012). Quantitative regional and ultrastructural localization of the Ca(v)2.3 subunit of R-type calcium channel in mouse brain. J. Neurosci. 32, 13555–13567. 10.1523/JNEUROSCI.1142-12.2012 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Pelegrin P., Barroso-Gutierrez C., Surprenant A. (2008). P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage. J. Immunol. 180, 7147–7157. 10.4049/jimmunol.180.11.7147 [Abstract] [CrossRef] [Google Scholar]
Pelisch N., Gomes C., Nally J. M., Petruska J. C., Stirling D. P. (2017). Differential expression of ryanodine receptor isoforms after spinal cord injury. Neurosci. Lett. 660, 51–56. 10.1016/j.neulet.2017.09.018 [Abstract] [CrossRef] [Google Scholar]
Perez-Reyes E. (2003). Molecular physiology of low-voltage-activated t-type calcium channels. Physiol. Rev. 83, 117–161. 10.1152/physrev.00018.2002 [Abstract] [CrossRef] [Google Scholar]
Pessia M., Imbrici P., D'Adamo M. C., Salvatore L., Tucker S. J. (2001). Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1. J. Physiol. 532 (Pt. 2), 359–367. 10.1111/j.1469-7793.2001.0359f.x [Abstract] [CrossRef] [Google Scholar]
Pietrobon D. (2010). CaV2.1 channelopathies. Pflugers Arch. 460, 375–393. 10.1007/s00424-010-0802-8 [Abstract] [CrossRef] [Google Scholar]
Pitman K. A., Ricci R., Gasperini R., Beasley S., Pavez M., Charlesworth J., et al. . (2020). The voltage-gated calcium channel CaV1.2 promotes adult oligodendrocyte progenitor cell survival in the mouse corpus callosum but not motor cortex. Glia 68, 376–392. 10.1002/glia.23723 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Poet M., Kornak U., Schweizer M., Zdebik A. A., Scheel O., Hoelter S., et al. . (2006). Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. Proc. Natl. Acad. Sci. U.S.A. 103, 13854–13859. 10.1073/pnas.0606137103 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Poopalasundaram S., Knott C., Shamotienko O. G., Foran P. G., Dolly J. O., Ghiani C. A., et al. . (2000). Glial heterogeneity in expression of the inwardly rectifying K(+) channel, Kir4.1, in adult rat CNS. Glia 30, 362–372. 10.1002/(sici)1098-1136(200006)30:4<362::aid-glia50>3.0.co;2-4 [Abstract] [CrossRef] [Google Scholar]
Prasad A., Teh D. B. L., Blasiak A., Chai C., Wu Y., Gharibani P. M., et al. . (2017). Static magnetic field stimulation enhances oligodendrocyte differentiation and secretion of neurotrophic factors. Sci. Rep. 7:6743. 10.1038/s41598-017-06331-8 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Pressey S. N., O'Donnell K. J., Stauber T., Fuhrmann J. C., Tyynela J., Jentsch T. J., et al. . (2010). Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1. J. Neuropathol. Exp. Neurol. 69, 1228–1246. 10.1097/NEN.0b013e3181ffe742 [Abstract] [CrossRef] [Google Scholar]
Qi H., Moran M. M., Navarro B., Chong J. A., Krapivinsky G., Krapivinsky L., et al. . (2007). All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proc. Natl. Acad. Sci. U.S.A. 104, 1219–1223. 10.1073/pnas.0610286104 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Raap M., Biedermann B., Braun P., Milenkovic I., Skatchkov S. N., Bringmann A., et al. . (2002). Diversity of Kir channel subunit mRNA expressed by retinal glial cells of the guinea-pig. Neuroreport 13, 1037–1040. 10.1097/00001756-200206120-00012 [Abstract] [CrossRef] [Google Scholar]
Rajakulendran S., Kaski D., Hanna M. G. (2012). Neuronal P/Q-type calcium channel dysfunction in inherited disorders of the CNS. Nat. Rev. Neurol. 8, 86–96. 10.1038/nrneurol.2011.228 [Abstract] [CrossRef] [Google Scholar]
Rasband M. N., Kagawa T., Park E. W., Ikenaka K., Trimmer J. S. (2003). Dysregulation of axonal sodium channel isoforms after adult-onset chronic demyelination. J. Neurosci. Res. 73, 465–470. 10.1002/jnr.10675 [Abstract] [CrossRef] [Google Scholar]
Rasmussen H. B., Trimmer J. S. (2019). The Voltage-Dependent K+ Channel Family. Oxford: Oxford University Press. [Google Scholar]
Reese K. A., Caldwell J. H. (1999). Immunocytochemical localization of NaCh6 in cultured spinal cord astrocytes. Glia 26, 92–96. 10.1002/(sici)1098-1136(199903)26:1<92::aid-glia10>3.0.co;2-4 [Abstract] [CrossRef] [Google Scholar]
Rettig J., Sheng Z. H., Kim D. K., Hodson C. D., Snutch T. P., Catterall W. A. (1996). Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25. Proc. Natl. Acad. Sci. U.S.A. 93, 7363–7368. 10.1073/pnas.93.14.7363 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Riccio A., Medhurst A. D., Mattei C., Kelsell R. E., Calver A. R., Randall A. D., et al. . (2002). mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Brain Res. Mol. Brain Res. 109, 95–104. 10.1016/s0169-328x(02)00527-2 [Abstract] [CrossRef] [Google Scholar]
Rivat C., Sar C., Mechaly I., Leyris J. P., Diouloufet L., Sonrier C., et al. . (2018). Inhibition of neuronal FLT3 receptor tyrosine kinase alleviates peripheral neuropathic pain in mice. Nat Commun 9, 1042. 10.1038/s41467-018-03496-2 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Rivera-Pagan A. F., Rivera-Aponte D. E., Melnik-Martinez K. V., Zayas-Santiago A., Kucheryavykh L. Y., Martins A. H., et al. . (2015). Up-regulation of TREK-2 potassium channels in cultured astrocytes requires de novo protein synthesis: relevance to localization of TREK-2 channels in astrocytes after transient cerebral ischemia. PLoS ONE. 10:e0125195. 10.1371/journal.pone.0125195 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Rizzi S., Knaus H. G., Schwarzer C. (2016). Differential distribution of the sodium-activated potassium channels slick and slack in mouse brain. J. Comp. Neurol. 524, 2093–2116. 10.1002/cne.23934 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Rommer P. S., Milo R., Han M. H., Satyanarayan S., Sellner J., Hauer L., et al. . (2019). Immunological aspects of approved MS therapeutics. Front. Immunol. 10:1564. 10.3389/fimmu.2019.01564 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Rui Y., Pollitt S. L., Myers K. R., Feng Y., Zheng J. Q. (2020). Spontaneous local calcium transients regulate oligodendrocyte development in culture through store-operated Ca(2+) entry and release. eNeuro 7. 10.1523/ENEURO.0347-19.2020 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Ruiz A., Matute C., Alberdi E. (2010). Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes. Cell Death Dis. 1:e54. 10.1038/cddis.2010.31 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Sadovnick A. D., Traboulsee A. L., Zhao Y., Bernales C. Q., Encarnacion M., Ross J. P., et al. . (2017). Genetic modifiers of multiple sclerosis progression, severity and onset. Clin. Immunol. 180, 100–105. 10.1016/j.clim.2017.05.009 [Abstract] [CrossRef] [Google Scholar]
Saegusa H., Kurihara T., Zong S., Minowa O., Kazuno A., Han W., et al. . (2000). Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel. Proc. Natl. Acad. Sci. U.S.A. 97, 6132–6137. 10.1073/pnas.100124197 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Saez J. C., Berthoud V. M., Branes M. C., Martinez A. D., Beyer E. C. (2003). Plasma membrane channels formed by connexins: their regulation and functions. Physiol. Rev. 83, 1359–1400. 10.1152/physrev.00007.2003 [Abstract] [CrossRef] [Google Scholar]
Sahu G., Sukumaran S., Bera A. K. (2014). Pannexins form gap junctions with electrophysiological and pharmacological properties distinct from connexins. Sci. Rep. 4:4955. 10.1038/srep04955 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Salinas M., de Weille J., Guillemare E., Lazdunski M., Hugnot J. P. (1997a). Modes of regulation of shab K+ channel activity by the Kv8.1 subunit. J. Biol. Chem. 272, 8774–8780. 10.1074/jbc.272.13.8774 [Abstract] [CrossRef] [Google Scholar]
Salinas M., Duprat F., Heurteaux C., Hugnot J. P., Lazdunski M. (1997b). New modulatory alpha subunits for mammalian Shab K+ channels. J. Biol. Chem. 272, 24371–24379. 10.1074/jbc.272.39.24371 [Abstract] [CrossRef] [Google Scholar]
Santiago Gonzalez D. A., Cheli V. T., Zamora N. N., Lama T. N., Spreuer V., Murphy G. G., et al. . (2017). Conditional deletion of the L-type calcium channel Cav1.2 in NG2-positive cells impairs remyelination in mice. J. Neurosci. 37, 10038–10051. 10.1523/JNEUROSCI.1787-17.2017 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Sappington R. M., Calkins D. J. (2008). Contribution of TRPV1 to microglia-derived IL-6 and NFkappaB translocation with elevated hydrostatic pressure. Invest Ophthalmol. Vis. Sci. 49, 3004–3017. 10.1167/iovs.07-1355 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Schampel A., Volovitch O., Koeniger T., Scholz C. J., Jorg S., Linker R. A., et al. . (2017). Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis. Proc. Natl. Acad. Sci. U.S.A. 114, E3295–E3304. 10.1073/pnas.1620052114 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Schattling B., Eggert B., Friese M. A. (2014). Acquired channelopathies as contributors to development and progression of multiple sclerosis. Exp. Neurol. 262 (Pt. A), 28–36. 10.1016/j.expneurol.2013.12.006 [Abstract] [CrossRef] [Google Scholar]
Schattling B., Fazeli W., Engeland B., Liu Y., Lerche H., Isbrandt D., et al. . (2016). Activity of NaV1.2 promotes neurodegeneration in an animal model of multiple sclerosis. JCI Insight 1:e89810. 10.1172/jci.insight.89810 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Scheffer I. E., Nabbout R. (2019). SCN1A-related phenotypes: epilepsy and beyond. Epilepsia 60 (Suppl. 3), S17–S24. 10.1111/epi.16386 [Abstract] [CrossRef] [Google Scholar]
Schilling T., Eder C. (2009). Importance of the non-selective cation channel TRPV1 for microglial reactive oxygen species generation. J. Neuroimmunol. 216, 118–121. 10.1016/j.jneuroim.2009.07.008 [Abstract] [CrossRef] [Google Scholar]
Schirmer L., Mobius W., Zhao C., Cruz-Herranz A., Ben Haim L., Cordano C., et al. . (2018). Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity. Elife 7:e36428. 10.7554/eLife.36428 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Schirmer L., Srivastava R., Kalluri S. R., Bottinger S., Herwerth M., Carassiti D., et al. . (2014). Differential loss of KIR4.1 immunoreactivity in multiple sclerosis lesions. Ann. Neurol. 75, 810–828. 10.1002/ana.24168 [Abstract] [CrossRef] [Google Scholar]
Schirmer L., Velmeshev D., Holmqvist S., Kaufmann M., Werneburg S., Jung D., et al. . (2019). Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature 573, 75–82. 10.1038/s41586-019-1404-z [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Schlichter L. C., Kaushal V., Moxon-Emre I., Sivagnanam V., Vincent C. (2010). The Ca2+ activated SK3 channel is expressed in microglia in the rat striatum and contributes to microglia-mediated neurotoxicity in vitro. J. Neuroinflammation 7:4. 10.1186/1742-2094-7-4 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Schmidt K., Eulitz D., Veh R. W., Kettenmann H., Kirchhoff F. (1999). Heterogeneous expression of voltage-gated potassium channels of the shaker family (Kv1) in oligodendrocyte progenitors. Brain Res. 843, 145–160. 10.1016/s0006-8993(99)01938-1 [Abstract] [CrossRef] [Google Scholar]
Schrey M., Codina C., Kraft R., Beetz C., Kalff R., Wolfl S., et al. . (2002). Molecular characterization of voltage-gated sodium channels in human gliomas. Neuroreport 13, 2493–2498. 10.1097/00001756-200212200-00023 [Abstract] [CrossRef] [Google Scholar]
Schulien A. J., Yeh C. Y., Orange B. N., Pav O. J., Hopkins M. P., Moutal A., et al. . (2020). Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels. Sci. Adv. 6:eaaz8110. 10.1126/sciadv.aaz8110 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Sedmak G., Judas M. (2021). White matter interstitial neurons in the adult human brain: 3% of cortical neurons in quest for recognition. Cells 10:190. 10.3390/cells10010190 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Sesti F., Wu X., Liu S. (2014). Oxidation of KCNB1 K(+) channels in central nervous system and beyond. World J. Biol. Chem. 5, 85–92. 10.4331/wjbc.v5.i2.85 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Shang K. W., Zhang Y. H., Yang X. L., Liu A. J., Yang Z. X., Liu X. Y., et al. . (2016). [Clinical features and gene mutations in epilepsy of infancy with migrating focal seizures]. Zhonghua Er Ke Za Zhi 54, 735–739. 10.3760/cma.j.issn.0578-1310.2016.10.005 [Abstract] [CrossRef] [Google Scholar]
Simpson P. B., Holtzclaw L. A., Langley D. B., Russell J. T. (1998). Characterization of ryanodine receptors in oligodendrocytes, type 2 astrocytes, and O-2A progenitors. J Neurosci. Res. 52, 468–482. 10.1002/(SICI)1097-4547(19980515)52:4<468::AID-JNR11>3.0.CO;2-# [Abstract] [CrossRef] [Google Scholar]
Sinha K., Karimi-Abdolrezaee S., Velumian A. A., Fehlings M. G. (2006). Functional changes in genetically dysmyelinated spinal cord axons of shiverer mice: role of juxtaparanodal Kv1 family K+ channels. J. Neurophysiol. 95, 1683–1695. 10.1152/jn.00899.2005 [Abstract] [CrossRef] [Google Scholar]
Sita G., Hrelia P., Graziosi A., Ravegnini G., Morroni F. (2018). TRPM2 in the brain: role in health and disease. Cells 7:82. 10.3390/cells7070082 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Siwek M. E., Muller R., Henseler C., Broich K., Papazoglou A., Weiergraber M. (2014). The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture. Sleep 37, 881–892. 10.5665/sleep.3652 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Smart S. L., Bosma M. M., Tempel B. L. (1997). Identification of the delayed rectifier potassium channel, Kv1.6, in cultured astrocytes. Glia 20, 127–134. 10.1002/(sici)1098-1136(199706)20:2<127::aid-glia4>3.0.co;2-6 [Abstract] [CrossRef] [Google Scholar]
Smith R. S., Kenny C. J., Ganesh V., Jang A., Borges-Monroy R., Partlow J. N., et al. . (2018). Sodium channel SCN3A (NaV1.3) regulation of human cerebral cortical folding and oral motor development. Neuron 99, 905–913.e907. 10.1016/j.neuron.2018.07.052 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
So K., Haraguchi K., Asakura K., Isami K., Sakimoto S., Shirakawa H., et al. . (2015). Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models. J. Pharmacol. Sci. 127, 237–243. 10.1016/j.jphs.2014.10.003 [Abstract] [CrossRef] [Google Scholar]
Soldovieri M. V., Miceli F., Taglialatela M. (2011). Driving with no brakes: molecular pathophysiology of Kv7 potassium channels. Physiology 26, 365–376. 10.1152/physiol.00009.2011 [Abstract] [CrossRef] [Google Scholar]
Sosinsky G. E., Boassa D., Dermietzel R., Duffy H. S., Laird D. W., MacVicar B., et al. . (2011). Pannexin channels are not gap junction hemichannels. Channels 5, 193–197. 10.4161/chan.5.3.15765 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Stampanoni Bassi M., Gentile A., Iezzi E., Zagaglia S., Musella A., Simonelli I., et al. . (2019). Transient receptor potential vanilloid 1 modulates central inflammation in multiple sclerosis. Front. Neurol. 10:30. 10.3389/fneur.2019.00030 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Stanika R., Campiglio M., Pinggera A., Lee A., Striessnig J., Flucher B. E., et al. . (2016). Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology. Sci. Rep. 6:34528. 10.1038/srep34528 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Stirling D. P., Cummins K., Wayne Chen S. R., Stys P. (2014). Axoplasmic reticulum Ca(2+) release causes secondary degeneration of spinal axons. Ann. Neurol. 75, 220–229. 10.1002/ana.24099 [Abstract] [CrossRef] [Google Scholar]
Stirling D. P., Stys P. K. (2010). Mechanisms of axonal injury: internodal nanocomplexes and calcium deregulation. Trends. Mol. Med. 16, 160–170. 10.1016/j.molmed.2010.02.002 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Stocker M. (2004). Ca(2+)-activated K+ channels: molecular determinants and function of the SK family. Nat. Rev. Neurosci. 5, 758–770. 10.1038/nrn1516 [Abstract] [CrossRef] [Google Scholar]
Striessnig J., Pinggera A., Kaur G., Bock G., Tuluc P. (2014). L-type Ca(2+) channels in heart and brain. Wiley Interdiscip. Rev. Membr. Transp. Signal 3, 15–38. 10.1002/wmts.102 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Subramanian N., Wetzel A., Dombert B., Yadav P., Havlicek S., Jablonka S., et al. . (2012). Role of Na(v)1.9 in activity-dependent axon growth in motoneurons. Hum. Mol. Genet. 21, 3655–3667. 10.1093/hmg/dds195 [Abstract] [CrossRef] [Google Scholar]
Sukiasyan N., Hultborn H., Zhang M. (2009). Distribution of calcium channel Ca(V)1.3 immunoreactivity in the rat spinal cord and brain stem. Neuroscience 159, 217–235. 10.1016/j.neuroscience.2008.12.011 [Abstract] [CrossRef] [Google Scholar]
Surmeier D. J., Mermelstein P. G., Goldowitz D. (1996). The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells. Proc. Natl. Acad. Sci. U.S.A. 93, 11191–11195. 10.1073/pnas.93.20.11191 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Suzuki S., Rogawski M. A. (1989). T-type calcium channels mediate the transition between tonic and phasic firing in thalamic neurons. Proc. Natl. Acad. Sci. U.S.A. 86, 7228–7232. 10.1073/pnas.86.18.7228 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Swayne L. A., Sorbara C. D., Bennett S. A. (2010). Pannexin 2 is expressed by postnatal hippocampal neural progenitors and modulates neuronal commitment. J. Biol. Chem. 285, 24977–24986. 10.1074/jbc.M110.130054 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Takahashi H., Magee J. C. (2009). Pathway interactions and synaptic plasticity in the dendritic tuft regions of CA1 pyramidal neurons. Neuron 62, 102–111. 10.1016/j.neuron.2009.03.007 [Abstract] [CrossRef] [Google Scholar]
Takahashi Y., Jeong S. Y., Ogata K., Goto J., Hashida H., Isahara K., et al. . (2003). Human skeletal muscle calcium channel alpha1S is expressed in the basal ganglia: distinctive expression pattern among L-type Ca2+ channels. Neurosci. Res. 45, 129–137. 10.1016/s0168-0102(02)00204-3 [Abstract] [CrossRef] [Google Scholar]
Takeuchi H., Suzumura A. (2014). Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases. Front. Cell Neurosci. 8:189. 10.3389/fncel.2014.00189 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Talley E. M., Solorzano G., Lei Q., Kim D., Bayliss D. A. (2001). Cns distribution of members of the two-pore-domain (KCNK) potassium channel family. J. Neurosci. 21, 7491–7505. 10.1523/JNEUROSCI.21-19-07491.2001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Tanemoto M., Fujita A., Higashi K., Kurachi Y. (2002). PSD-95 mediates formation of a functional homomeric Kir5.1 channel in the brain. Neuron 34, 387–397. 10.1016/s0896-6273(02)00675-x [Abstract] [CrossRef] [Google Scholar]
Tanemoto M., Kittaka N., Inanobe A., Kurachi Y. (2000). In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1. J. Physiol. 525 (Pt. 3), 587–592. 10.1111/j.1469-7793.2000.00587.x [Abstract] [CrossRef] [Google Scholar]
Taruno A. (2018). ATP release channels. Int. J. Mol. Sci. 19:808. 10.3390/ijms19030808 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Theis M., Sohl G., Eiberger J., Willecke K. (2005). Emerging complexities in identity and function of glial connexins. Trends Neurosci. 28, 188–195. 10.1016/j.tins.2005.02.006 [Abstract] [CrossRef] [Google Scholar]
Thiffault I., Speca D. J., Austin D. C., Cobb M. M., Eum K. S., Safina N. P., et al. . (2015). A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization. J. Gen. Physiol. 146, 399–410. 10.1085/jgp.201511444 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Thimmapaya R., Neelands T., Niforatos W., Davis-Taber R. A., Choi W., Putman C. B., et al. . (2005). Distribution and functional characterization of human Nav1.3 splice variants. Eur. J. Neurosci. 22, 1–9. 10.1111/j.1460-9568.2005.04155.x [Abstract] [CrossRef] [Google Scholar]
Thorell W. E., Leibrock L. G., Agrawal S. K. (2002). Role of RyRs and IP3 receptors after traumatic injury to spinal cord white matter. J. Neurotrauma 19, 335–342. 10.1089/089771502753594909 [Abstract] [CrossRef] [Google Scholar]
Tippens A. L., Pare J. F., Langwieser N., Moosmang S., Milner T. A., Smith Y., et al. . (2008). Ultrastructural evidence for pre- and postsynaptic localization of Cav1.2 L-type Ca2+ channels in the rat hippocampus. J. Comp. Neurol. 506, 569–583. 10.1002/cne.21567 [Abstract] [CrossRef] [Google Scholar]
Toriyama H., Wang L., Saegusa H., Zong S., Osanai M., Murakoshi T., et al. . (2002). Role of Ca(v) 2.3 (alpha1E) Ca2+ channel in ischemic neuronal injury. Neuroreport 13, 261–265. 10.1097/00001756-200202110-00018 [Abstract] [CrossRef] [Google Scholar]
Torkamani A., Bersell K., Jorge B. S., Bjork R. L., Jr., Friedman J. R., Bloss C. S., et al. . (2014). De novo KCNB1 mutations in epileptic encephalopathy. Ann. Neurol. 76, 529–540. 10.1002/ana.24263 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Trebak M., Kinet J. P. (2019). Calcium signalling in T cells. Nat. Rev. Immunol. 19, 154–169. 10.1038/s41577-018-0110-7 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Trimmer J. S. (2015). Subcellular localization of K+ channels in mammalian brain neurons: remarkable precision in the midst of extraordinary complexity. Neuron 85, 238–256. 10.1016/j.neuron.2014.12.042 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Trimmer J. S., Rhodes K. J. (2004). Localization of voltage-gated ion channels in mammalian brain. Annu. Rev. Physiol. 66, 477–519. 10.1146/annurev.physiol.66.032102.113328 [Abstract] [CrossRef] [Google Scholar]
Tsuji F., Murai M., Oki K., Seki I., Ueda K., Inoue H., et al. . (2010). Transient receptor potential vanilloid 1 agonists as candidates for anti-inflammatory and immunomodulatory agents. Eur. J. Pharmacol. 627, 332–339. 10.1016/j.ejphar.2009.10.044 [Abstract] [CrossRef] [Google Scholar]
Tsutsui M., Hirase R., Miyamura S., Nagayasu K., Nakagawa T., Mori Y., et al. . (2018). TRPM2 exacerbates central nervous system inflammation in experimental autoimmune encephalomyelitis by increasing production of CXCL2 chemokines. J. Neurosci. 38, 8484–8495. 10.1523/JNEUROSCI.2203-17.2018 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Tucker S. J., Imbrici P., Salvatore L., D'Adamo M. C., Pessia M. (2000). pH dependence of the inwardly rectifying potassium channel, Kir5.1, and localization in renal tubular epithelia. J. Biol. Chem. 275, 16404–16407. 10.1074/jbc.C000127200 [Abstract] [CrossRef] [Google Scholar]
Tzingounis A. V., Heidenreich M., Kharkovets T., Spitzmaul G., Jensen H. S., Nicoll R. A., et al. . (2010). The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus. Proc. Natl. Acad. Sci. U.S.A. 107, 10232–10237. 10.1073/pnas.1004644107 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Tzour A., Leibovich H., Barkai O., Biala Y., Lev S., Yaari Y., et al. . (2017). KV 7/M channels as targets for lipopolysaccharide-induced inflammatory neuronal hyperexcitability. J. Physiol. 595, 713–738. 10.1113/JP272547 [Abstract] [CrossRef] [Google Scholar]
Vacher H., Mohapatra D. P., Trimmer J. S. (2008). Localization and targeting of voltage-dependent ion channels in mammalian central neurons. Physiol. Rev. 88, 1407–1447. 10.1152/physrev.00002.2008 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
van de Graaf S. F., Hoenderop J. G., Bindels R. J. (2006). Regulation of TRPV5 and TRPV6 by associated proteins. Am. J. Physiol. Renal Physiol. 290, F1295–1302. 10.1152/ajprenal.00443.2005 [Abstract] [CrossRef] [Google Scholar]
Van Der Stelt M., Di Marzo V. (2004). Endovanilloids. Putative endogenous ligands of transient receptor potential vanilloid 1 channels. Eur. J. Biochem. 271, 1827–1834. 10.1111/j.1432-1033.2004.04081.x [Abstract] [CrossRef] [Google Scholar]
Vanderver A., Simons C., Schmidt J. L., Pearl P. L., Bloom M., Lavenstein B., et al. . (2014). Identification of a novel de novo p.Phe932Ile KCNT1 mutation in a patient with leukoencephalopathy and severe epilepsy. Pediatr. Neurol. 50, 112–114. 10.1016/j.pediatrneurol.2013.06.024 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Vasistha N. A., Johnstone M., Barton S. K., Mayerl S. E., Thangaraj Selvaraj B., Thomson P. A., et al. . (2019). Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte-myelin dysfunction. Mol. Psychiatry 24, 1641–1654. 10.1038/s41380-019-0505-2 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Vautier F., Belachew S., Chittajallu R., Gallo V. (2004). Shaker-type potassium channel subunits differentially control oligodendrocyte progenitor proliferation. Glia 48, 337–345. 10.1002/glia.20088 [Abstract] [CrossRef] [Google Scholar]
Vay S. U., Flitsch L. J., Rabenstein M., Moniere H., Jakovcevski I., Andjus P., et al. . (2020). The impact of hyperpolarization-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium KCNQ/Kv7 channels on primary microglia function. J. Neuroinflammation 17:100. 10.1186/s12974-020-01779-4 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Veng L. M., Mesches M. H., Browning M. D. (2003). Age-related working memory impairment is correlated with increases in the L-type calcium channel protein alpha1D (Cav1.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment. Brain Res. Mol. Brain Res. 110, 193–202. 10.1016/s0169-328x(02)00643-5 [Abstract] [CrossRef] [Google Scholar]
Vennekens R., Hoenderop J. G., Prenen J., Stuiver M., Willems P. H., Droogmans G., et al. . (2000). Permeation and gating properties of the novel epithelial Ca(2+) channel. J. Biol. Chem. 275, 3963–3969. 10.1074/jbc.275.6.3963 [Abstract] [CrossRef] [Google Scholar]
Vierra N. C., Kirmiz M., van der List D., Santana L. F., Trimmer J. S. (2019). Kv2.1 mediates spatial and functional coupling of L-type calcium channels and ryanodine receptors in mammalian neurons. Elife 8:e49953. 10.7554/eLife.49953 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Vigil F. A., Bozdemir E., Bugay V., Chun S. H., Hobbs M., Sanchez I., et al. . (2020). Prevention of brain damage after traumatic brain injury by pharmacological enhancement of KCNQ (Kv7, “M-type”) K(+) currents in neurons. J. Cereb. Blood Flow Metab. 40, 1256–1273. 10.1177/0271678X19857818 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Villegas R., Martinez N. W., Lillo J., Pihan P., Hernandez D., Twiss J. L., et al. . (2014). Calcium release from intra-axonal endoplasmic reticulum leads to axon degeneration through mitochondrial dysfunction. J. Neurosci. 34, 7179–7189. 10.1523/JNEUROSCI.4784-13.2014 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Vogt A., Hormuzdi S. G., Monyer H. (2005). Pannexin1 and Pannexin2 expression in the developing and mature rat brain. Brain Res. Mol. Brain Res. 141, 113–120. 10.1016/j.molbrainres.2005.08.002 [Abstract] [CrossRef] [Google Scholar]
Wainger B. J., Kiskinis E., Mellin C., Wiskow O., Han S. S., Sandoe J., et al. . (2014). Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 7, 1–11. 10.1016/j.celrep.2014.03.019 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wang H., Allen M. L., Grigg J. J., Noebels J. L., Tempel B. L. (1995). Hypomyelination alters K+ channel expression in mouse mutants shiverer and Trembler. Neuron 15, 1337–1347. 10.1016/0896-6273(95)90012-8 [Abstract] [CrossRef] [Google Scholar]
Wang H., Kunkel D. D., Martin T. M., Schwartzkroin P. A., Tempel B. L. (1993). Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons. Nature 365, 75–79. 10.1038/365075a0 [Abstract] [CrossRef] [Google Scholar]
Wang H., Zhang X., Xue L., Xing J., Jouvin M. H., Putney J. W., et al. . (2016). Low-Voltage-Activated CaV3.1 calcium channels shape T helper cell cytokine profiles. Immunity 44, 782–794. 10.1016/j.immuni.2016.01.015 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wang H. S., Pan Z., Shi W., Brown B. S., Wymore R. S., Cohen I. S., et al. . (1998). KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282, 1890–1893. 10.1126/science.282.5395.1890 [Abstract] [CrossRef] [Google Scholar]
Wang J., Ou S. W., Wang Y. J. (2017). Distribution and function of voltage-gated sodium channels in the nervous system. Channels 11, 534–554. 10.1080/19336950.2017.1380758 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wang K., Lin M. T., Adelman J. P., Maylie J. (2014). Distinct Ca2+ sources in dendritic spines of hippocampal CA1 neurons couple to SK and Kv4 channels. Neuron 81, 379–387. 10.1016/j.neuron.2013.11.004 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wang N., De Bock M., Decrock E., Bol M., Gadicherla A., Vinken M., et al. . (2013). Paracrine signaling through plasma membrane hemichannels. Biochim. Biophys. Acta 1828, 35–50. 10.1016/j.bbamem.2012.07.002 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wang R., Tu S., Zhang J., Shao A. (2020). Roles of TRP channels in neurological diseases. Oxid. Med. Cell Longev. 2020:7289194. 10.1155/2020/7289194 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wang W., Gao X. F., Xiao L., Xiang Z. H., He C. (2011). K(V)7/KCNQ channels are functionally expressed in oligodendrocyte progenitor cells. PLoS ONE 6:e21792. 10.1371/journal.pone.0021792 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wartosch L., Fuhrmann J. C., Schweizer M., Stauber T., Jentsch T. J. (2009). Lysosomal degradation of endocytosed proteins depends on the chloride transport protein ClC-7. FASEB J. 23, 4056–4068. 10.1096/fj.09-130880 [Abstract] [CrossRef] [Google Scholar]
Watanabe M., Ueda T., Shibata Y., Kumamoto N., Shimada S., Ugawa S. (2015). Expression and regulation of Cav3.2 T-Type calcium channels during inflammatory hyperalgesia in mouse dorsal root ganglion neurons. PLoS ONE 10:e0127572. 10.1371/journal.pone.0127572 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Waxman S. G. (2001). Acquired channelopathies in nerve injury and MS. Neurology 56, 1621–1627. 10.1212/wnl.56.12.1621 [Abstract] [CrossRef] [Google Scholar]
Weiergraber M., Henry M., Radhakrishnan K., Hescheler J., Schneider T. (2007). Hippocampal seizure resistance and reduced neuronal excitotoxicity in mice lacking the Cav2.3 E/R-type voltage-gated calcium channel. J. Neurophysiol. 97, 3660–3669. 10.1152/jn.01193.2006 [Abstract] [CrossRef] [Google Scholar]
Weinert S., Jabs S., Hohensee S., Chan W. L., Kornak U., Jentsch T. J. (2014). Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions. EMBO Rep. 15, 784–791. 10.15252/embr.201438553 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Weinreich F., Jentsch T. J. (2001). Pores formed by single subunits in mixed dimers of different CLC chloride channels. J. Biol. Chem. 276, 2347–2353. 10.1074/jbc.M005733200 [Abstract] [CrossRef] [Google Scholar]
Weiss N., Zamponi G. W. (2019). T-type calcium channels: from molecule to therapeutic opportunities. Int. J. Biochem. Cell Biol. 108, 34–39. 10.1016/j.biocel.2019.01.008 [Abstract] [CrossRef] [Google Scholar]
Westenbroek R. E., Noebels J. L., Catterall W. A. (1992). Elevated expression of type II Na+ channels in hypomyelinated axons of shiverer mouse brain. J. Neurosci. 12, 2259–2267 [Europe PMC free article] [Abstract] [Google Scholar]
Wetzel A., Jablonka S., Blum R. (2013). Cell-autonomous axon growth of young motoneurons is triggered by a voltage-gated sodium channel. Channels 7, 51–56. 10.4161/chan.23153 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Whitaker W. R., Faull R. L., Waldvogel H. J., Plumpton C. J., Emson P. C., Clare J. J. (2001). Comparative distribution of voltage-gated sodium channel proteins in human brain. Brain Res. Mol. Brain Res. 88, 37–53. 10.1016/s0169-328x(00)00289-8 [Abstract] [CrossRef] [Google Scholar]
Whyte-Fagundes P., Zoidl G. (2018). Mechanisms of pannexin1 channel gating and regulation. Biochim. Biophys. Acta Biomembr. 1860, 65–71. 10.1016/j.bbamem.2017.07.009 [Abstract] [CrossRef] [Google Scholar]
Willecke K., Eiberger J., Degen J., Eckardt D., Romualdi A., Guldenagel M., et al. . (2002). Structural and functional diversity of connexin genes in the mouse and human genome. Biol. Chem. 383, 725–737. 10.1515/BC.2002.076 [Abstract] [CrossRef] [Google Scholar]
Willis M., Kaufmann W. A., Wietzorrek G., Hutter-Paier B., Moosmang S., Humpel C., et al. . (2010). L-type calcium channel CaV 1.2 in transgenic mice overexpressing human AbetaPP751 with the London (V717I) and Swedish (K670M/N671L) mutations. J. Alzheimers Dis. 20, 1167–1180. 10.3233/JAD-2010-091117 [Abstract] [CrossRef] [Google Scholar]
Winter M., Weissgerber P., Klein K., Lux F., Yildiz D., Wissenbach U., et al. . (2020). Transient receptor potential vanilloid 6 (TRPV6) proteins control the extracellular matrix structure of the placental labyrinth. Int. J. Mol. Sci. 21:9674. 10.3390/ijms21249674 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Woo D. H., Han K. S., Shim J. W., Yoon B. E., Kim E., Bae J. Y., et al. . (2012). TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell 151, 25–40. 10.1016/j.cell.2012.09.005 [Abstract] [CrossRef] [Google Scholar]
Wormuth C., Lundt A., Henseler C., Muller R., Broich K., Papazoglou A., et al. . (2016). Review: Cav2.3 R-type voltage-gated Ca(2+) channels - functional implications in convulsive and non-convulsive seizure activity. Open Neurol. J. 10, 99–126. 10.2174/1874205X01610010099 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Wu C. Y., Kaur C., Sivakumar V., Lu J., Ling E. A. (2009). Kv1.1 expression in microglia regulates production and release of proinflammatory cytokines, endothelins and nitric oxide. Neuroscience 158, 1500–1508. 10.1016/j.neuroscience.2008.11.043 [Abstract] [CrossRef] [Google Scholar]
Wu L. G., Westenbroek R. E., Borst J. G., Catterall W. A., Sakmann B. (1999). Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses. J. Neurosci. 19, 726–736. [Europe PMC free article] [Abstract] [Google Scholar]
Wu Z., Li L., Xie F., Xu G., Dang D., Yang Q. (2020). Enhancing KCNQ channel activity improves neurobehavioral recovery after spinal cord injury. J. Pharmacol. Exp. Ther. 373, 72–80. 10.1124/jpet.119.264010 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Xiao K., Sun Z., Jin X., Ma W., Song Y., Lai S., et al. . (2018). ERG3 potassium channel-mediated suppression of neuronal intrinsic excitability and prevention of seizure generation in mice. J. Physiol. 596, 4729–4752. 10.1113/JP275970 [Abstract] [CrossRef] [Google Scholar]
Xiao Y., Lv X., Cao G., Bian G., Duan J., Ai J., et al. . (2010). Overexpression of Trpp5 contributes to cell proliferation and apoptosis probably through involving calcium homeostasis. Mol. Cell Biochem. 339, 155–161. 10.1007/s11010-009-0379-8 [Abstract] [CrossRef] [Google Scholar]
Xiao Z. S., Quarles L. D. (2010). Role of the polycytin-primary cilia complex in bone development and mechanosensing. Ann. N. Y. Acad. Sic. 1192, 410–421. 10.1111/j.1749-6632.2009.05239.x [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Xu H., Tian W., Fu Y., Oyama T. T., Anderson S., Cohen D. M. (2007). Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene. Am. J. Physiol. Renal Physiol. 293, F1865–1876. 10.1152/ajprenal.00347.2007 [Abstract] [CrossRef] [Google Scholar]
Xu J. H., Long L., Tang Y. C., Hu H. T., Tang F. R. (2007). Ca(v)1.2, Ca(v)1.3, and Ca(v)2.1 in the mouse hippocampus during and after pilocarpine-induced status epilepticus. Hippocampus 17, 235–251. 10.1002/hipo.20263 [Abstract] [CrossRef] [Google Scholar]
Yan E., Li B., Gu L., Hertz L., Peng L. (2013). Mechanisms for L-channel-mediated increase in [Ca(2+)]i and its reduction by anti-bipolar drugs in cultured astrocytes combined with its mRNA expression in freshly isolated cells support the importance of astrocytic L-channels. Cell Calcium 54, 335–342. 10.1016/j.ceca.2013.08.002 [Abstract] [CrossRef] [Google Scholar]
Yasuda R., Sabatini B. L., Svoboda K. (2003). Plasticity of calcium channels in dendritic spines. Nat. Neurosci. 6, 948–955. 10.1038/nn1112 [Abstract] [CrossRef] [Google Scholar]
Yeung A. K., Patil C. S., Jackson M. F. (2020). Pannexin-1 in the CNS: emerging concepts in health and disease. J. Neurochem. 154, 468–485. 10.1111/jnc.15004 [Abstract] [CrossRef] [Google Scholar]
Yu F. H., Catterall W. A. (2003). Overview of the voltage-gated sodium channel family. Genome Biol. 4:207. 10.1186/gb-2003-4-3-207 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zamora N. N., Cheli V. T., Santiago Gonzalez D. A., Wan R., Paez P. M. (2020). Deletion of voltage-gated calcium channels in astrocytes during demyelination reduces brain inflammation and promotes myelin regeneration in mice. J. Neurosci. 40, 3332–3347. 10.1523/JNEUROSCI.1644-19.2020 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zamponi G. W., Striessnig J., Koschak A., Dolphin A. C. (2015). The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol. Rev. 67, 821–870. 10.1124/pr.114.009654 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zhang H., Maximov A., Fu Y., Xu F., Tang T. S., Tkatch T., et al. . (2005). Association of CaV1.3 L-type calcium channels with shank. J. Neurosci. 25, 1037–1049. 10.1523/JNEUROSCI.4554-04.2005 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zhang Y., Chen K., Sloan S. A., Bennett M. L., Scholze A. R., O'Keeffe S., et al. . (2014). An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929–11947. 10.1523/JNEUROSCI.1860-14.2014 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zhou J. Z., Jiang J. X. (2014). Gap junction and hemichannel-independent actions of connexins on cell and tissue functions–an update. FEBS Lett. 588, 1186–1192. 10.1016/j.febslet.2014.01.001 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zhou M., Xu G., Xie M., Zhang X., Schools G. P., Ma L., et al. . (2009). TWIK-1 and TREK-1 are potassium channels contributing significantly to astrocyte passive conductance in rat hippocampal slices. J. Neurosci. 29, 8551–8564. 10.1523/JNEUROSCI.5784-08.2009 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zhou W., Cayabyab F. S., Pennefather P. S., Schlichter L. C., DeCoursey T. E. (1998). HERG-like K+ channels in microglia. J. Gen. Physiol. 111, 781–794. 10.1085/jgp.111.6.781 [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]
Zou A., Lin Z., Humble M., Creech C. D., Wagoner P. K., Krafte D., et al. . (2003). Distribution and functional properties of human KCNH8 (Elk1) potassium channels. Am. J. Physiol. Cell Physiol. 285, C1356–1366. 10.1152/ajpcell.00179.2003 [Abstract] [CrossRef] [Google Scholar]
Zoupi L., Markoullis K., Kleopa K. A., Karagogeos D. (2013). Alterations of juxtaparanodal domains in two rodent models of CNS demyelination. Glia 61, 1236–1249. 10.1002/glia.22511 [Abstract] [CrossRef] [Google Scholar]
Zuccotti A., Clementi S., Reinbothe T., Torrente A., Vandael D. H., Pirone A. (2011). Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting. Trends Pharmacol. Sci. 32, 366–375. 10.1016/j.tips.2011.02.012 [Abstract] [CrossRef] [Google Scholar]

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Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

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Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Francesca Boscia

Maria Louise Elkjaer

Zsolt Illes

Maria Kukley

Abstract

Introduction

Table 1

Table 2

Table 3

K+ Channels

Voltage-Gated K+ Channels (Kv)

Kv1.1, Kv1.2, and Kv1.4 (KCNA1, KCNA2, and KCNA4)

Neurons

Glia

Expression and Function in MS

Kv2.1 and Kv2.2 (KCNB1 and KCNB2)

Neurons

Glia

Expression and Function in MS

Kv3.3 (KCNC3)

Neurons

Glia

Expression and Function in MS

Kv4.2 (KCND2)

Neurons

Glia

Expression and Function in MS

Kv7.2, Kv7.3, and Kv7.5 (KCNQ2, KCNQ3, and KCNQ5)

Neurons

Glia

Expression and Function in MS

Kv8.1 and Kv9.2 (KCNV1 and KCNS2)

Neurons

Glia

Expression and Function in MS

Eag2, erg3, and elk1 (KCNH5, KCNH7, and KCNH8)

Neurons

Glia

Expression and Function in MS

Two-Pore Domain K+ Channels (K2P)

TREK1 and TREK2 (KCNK2 and KCNK10)

Neurons and Glia

Expression and Function in MS

Na+- and Ca2+-Activated K+ Channels

KNa1.1 (KCNT1)

Neurons

Glia

Expression and Function in MS

KCa2.3, SK3 (KCNN3)

Neurons

Glia

Expression and Function in MS

Inward Rectifier K+ Channels (Kir)

Kir3.2 (KCNJ6)

Neurons

Glia

Expression and Function in MS

Kir5.1 (KCNJ16)

Neurons

Glia

Expression and Function in MS

Voltage-Gated Na+ Channels (Nav)

NaV1.1 (SCN1A)

Neurons

Glia

Expression and Function in MS

NaV1.2 (SCN2A)

Neurons

Glia

K⁺ Channels

Voltage-Gated K⁺ Channels (K_v)

K_v1.1, K_v1.2, and K_v1.4 (KCNA1, KCNA2, and KCNA4)

K_v3.3 (KCNC3)

K_v7.2, K_v7.3, and K_v7.5 (KCNQ2, KCNQ3, and KCNQ5)

K_v8.1 and K_v9.2 (KCNV1 and KCNS2)

Two-Pore Domain K⁺ Channels (K2P)

Na⁺- and Ca²⁺-Activated K⁺ Channels

K_Na1.1 (KCNT1)

K_Ca2.3, SK3 (KCNN3)

Inward Rectifier K⁺ Channels (K_ir)

Voltage-Gated Na⁺ Channels (Na_v)

Na_V1.1 (SCN1A)

Na_V1.2 (SCN2A)

Na_V1.3 (SCN3A)

Na_V1.6 (SCN8A)

Na_V1.9 (SCN11A)

Voltage-Gated Ca²⁺ Channels (VGCCs)

Ca_V1.2 (CACNA1C)

Ca_V1.3 (CACNA1D)

Ca_V2.1 (CACNA1A)

Ca_V2.3 (CACNA1E), R-Type VGCCs