KCNE3

Potassium voltage-gated channel, Isk-related family, member 3 (KCNE3), also known as MinK-related peptide 2 (MiRP2) is a protein that in humans is encoded by the KCNE3 gene.

Function

Voltage-gated potassium channels (K_v) represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. KCNE3 encodes a member of the five-strong KCNE family of voltage-gated potassium (K_v) channel ancillary or β subunits.

KCNE3 is best known for modulating the KCNQ1 K_v α subunit, but it also regulates hERG, K_v2.1, K_v3.x, K_v4.x and K_v12.2 in heterologous co-expression experiments and/or in vivo.

Co-assembly with KCNE3 converts KCNQ1 from a voltage-dependent delayed rectifier K+ channel to a constitutively open K+ channel with an almost linear current/voltage (I/V) relationship. KCNQ1-KCNE3 channels have been detected in the basolateral membrane of mouse small intestinal crypts, where they provide a driving force to regulate Cl- secretion. Specific amino acids within the transmembrane segment (V72) and extracellular domain (D54 and D55) of KCNE3 are important for its control of KCNQ1 voltage dependence. D54 and D55 interact electrostatically with R237 in the S4 segment of the KCNQ1 voltage sensor, helping to stabilize S4 in the activated state, which in turn locks open the channel unless the cell is held at a strongly hyperpolarizing (negative) membrane potential. The ability of KCNQ1-KCNE3 channels to remain open at weakly negative membrane potentials permits their activity in non-excitable, polarized epithelial cells such as those in the intestine.