Dr Matthew Ho

BSc(Med) MBBS(Hons) FANZCA

Cellular Physiology

Physiol-10A16 Describe the processes whereby substances may cross cell membranes, giving
examples

1. The cell membrane is a phospholipid bilayer which separates the ICF and ECF. It is selectively
permeable and transport across the cell membrane is necessary for cellular communication.

Method Example Mechanism

Passive diffusion Steroid hormones The random movements of substance across the cell membrane
O2, CO2 down its concentration gradient. The substance must be lipid
All ion channels soluble OR diffuse through specific channels and diffusion rate
Water occurs according to Ficks Law:
(aquaporins) 𝐒𝐨𝐥 𝐱 𝐀 𝐱 ∆𝐏
𝐃𝐢𝐟𝐟𝐮𝐬𝐢𝐨𝐧 =
√𝐌𝐖𝐱𝐓
The specific channels are gated to control diffusion:
Voltage gated (Ca channels in myocytes) – open by ↓RMP
Ligand gated (N ACh R) – opened by binding of ligand to receptor
Facilitated diffusion: Glucose The movement of a substance down its concentration gradient
Ion channels Amino acids through specific protein channels. Unlike passive diffusion, this
Aquaporins Na, K can become saturated and reaches a plateau maximum value.
Primary active Na/K-ATPase The movement of a substance against its concentration gradient
pump through an energy-consuming pump. The best example is the
Na/K-ATPase pump which uses ATP to pump 3Na out of the cell
and 2K into the cell.
Secondary active: The movement of a substance against its concentration gradient
Symport Na/glucose, Na/I using a gradient generated by the Na/K-ATPase pump.
Antiport Na/Ca, Na/H Co-transport is the movement in the same direction as the
transport molecule (down its concentration gradient)
Counter-transport is the movement in the opposite direction as
the transport molecule (down its concentration gradient)
Endocytosis Phagocytosis The process of ingestion of large particles into the cell by vesicle
Pinocytosis formation from the cell membrane.
Phagocytosis: ingestion of large molecule by vacuoles formed
from the cell membrane (PMN, macrophage) when an antibody
complex binds to a cell receptor
Pinocytosis: ingestion of smaller molecules (proteins)
Exocytosis Release of ACh at The process of extruding intracellular contents whereby vesicles
NMJ formed by Golgi apparatus containing material for export bind to
the cell membrane, emptying its contents. This requires entry
Ca2+ into the cell to cause fusion of membranes.
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

Physiol-06A12 Classify and describe the main cellular and molecular mechanisms by which chemical
neurotransmitters exert their effects. Use examples from cholinergic and adrenergic
neurotransmission to illustrate the answer.

1. A neurotransmitter is a chemical messenger which is released by a presynaptic cell on excitation

that crosses a synapse and binds to a receptor to stimulate or inhibit a post synaptic cell. They
can also be released to act on presynaptic receptors.

2. Mechanism of release:
a. Neurotransmitters are stored in presynaptic vesicles in the presynaptic nerve terminal
b. An AP (electrical stimulus) causes the release of Ca2+ which triggers exocytosis of the
vesicle and release of NT into the synaptic cleft.
c. The neurotransmitter diffuses across the membrane.

3. There are 2 main groups of neurotransmitter-receptor mechanisms:

a. Ion channels (Ionotrophic):
i. Structure: protein pores in the cell membrane which control passive flux of ions
down an electrochemical gradient.
ii. Mechanism: the binding of neurotransmitter to the ion channel directly
activates the channel (closed  open). Depending on the type of ion channel,
and the movement of ions, this tends to cause electrical activation
(depolarisation) or inactivation (hyperpolarisation). Due to direct effect, binding-
response is fast. In general:
1. Open K, Cl  inhibition (GABA)
2. Open Na, Ca  activation (Nicotinic)
b. G-protein coupled receptors:
i. Structure: serpentine protein with 7 helical regions which traverse the
membrane with an extracellular amino end, and an intracellular carboxyl end.
Associated with Heterotrimetric G-protein. There are 5 families of GPCR, which
have characteristics defined by the nature of the α-subunit: Gs, Gi, Gq, GT, G12.
ii. Mechanism:
1. Binding of neurotransmitter to G protein receptor site
2. Activation of G-protein which triggers a conformational change: GDP
hydrolysed  GTP and the α-GTP complex detaches
3. α-GTP complex transverses the membrane to interact with an effector
enzyme to ↑ or ↓ production of a second messenger.
4. 2nd messengers change cell function by acting on other proteins,
enzymes or ion channels.

4. Specific examples of acetyl choline and adrenergic transmission

Receptor Type Mechanism Example

Nicotinic 5 sub-unit ACh binds to α subunits  NM channel at NMJ  sarcolemma
ACh receptor with conformational change  open of depolarisation  action potential
central cation cation pore  ↑ Na conductance (small  release of Ca by voltage gated
pore ↑Ca, K conductance) channels from sarcoplasmic
reticulum  excitation-contraction
M1 Gq coupled ACh binds GPCR  ↑PLC  ↑DAG/IP3 Parietal cells  muscle cell
 ↓K conductance depolarisation
M2 Gi coupled ACh binds GPCR  direct ↑K Conducting myocytes 
conductance hyperpolarisation  ↓ HR,
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

contractility
M3 Gq coupled ACh binds GPCR  ↑PLC  ↑DAG/IP3 GI smooth muscle 
 ↓K conductance depolarisation  contraction and
peristalsis
α1 Gq coupled Adrenaline binds GPCR  ↑PLC  Smooth muscle vessels 
↑DAG/IP3  ↑Ca conductance vasoconstriction
α2 Gi coupled Adrenaline binds GPCR  ↓adenylyl Presynaptic nerve endings  ↓
cyclase  ↓cAMP  ↓Ca conductance further release of NA (feedback
inhibition)
β1 GS coupled Adrenaline binds GPCR  ↑adenylyl Cardiac conduction system 
cyclase  ↑cAMP  ↑Na, Ca ↑heart rate, contractility
β2 GS coupled conductance (by phosphorylation of Pancreatic cells  ↑insulin release
β3 GS coupled sarcoplasmic reticulum channel by Adipose cells  ↑HSL activity
protein kinase A). (lipolysis)
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

Physiol-04B15/972 Describe the mechanism of action of G-proteins in the cell

1. G protein: a multi-unit membrane bound protein which exchanges GDP for GTP in order to bring
about a change in cellular function. It is an important mechanism of drug action whereby an
extracellular ligand can produce an amplified and/or regulated intracellular effect.

2. Structure:

a. Heterotrimetric protein consisting of α, β and γ subunits. The α subunit is attached at

rest to GDP. It lies on the cytosolic side of the membrane.
b. Attached to a G-protein coupled receptor. Serpentine structure with 7 helical regions
which traverse the membrane with an extracellular amino end, and an intracellular
carboxyl end.
c. Coupled with a cytoplasmic effector protein which catalyses the formation of 2nd
messenger proteins.

3. Mechanism:
a. Binding of extracellular ligand to the G protein receptor site
b. Binding activates the G-protein and triggers a conformational change:
i. The GDP hydrolysed  GTP and the α-GTP complex detaches
c. The α-GTP complex traverses the membrane to interact with the effector enzyme:
i. Increases or decrease production of second messenger
ii. The second messengers then change cell function via acting on other proteins,
enzymes or ion channels.

4. Specific properties
a. Amplification:
i. The ratio of G protein: GPCR = 100:1. Each G protein can catalyse multiple
effector enzymes. Thus extracellular binding of GPCR can be amplified by G
proteins to increase intracellular effect.
b. Regulation:
i. Inactivation occurs by intrinsic GTP-ase activity of α-subunit which reconverts
GTP  GDP, and recombines with βγ subunits.
ii. Second messenger levels are regulated by other enzymes which reform its
substrate. E.g. phosphodiesterase converts cAMP  ATP
iii. Binding of agonist can cause phosphorylation of the carboxyl terminal causes
binding of β-arrestin which signals removal of the G protein from the cell
membrane. This is an important mechanism of down regulation / tachyphylaxis.

5. Functions and Examples

G-protein Extracellular Effector enzymes 2nd messenger GPCR
type ligands
GS Catecholamines Adenylyl cyclase (ATP  cAMP  PKA Β1 adrenergic
cAMP) ADH, PTH
Gi opioid Adenylyl cyclase ↓cAMP  opens K μ receptor
inhibition  ↓cAMP channels
Gq ACh Phospholipase C (PIP2  IP3  ↑ Ca M1,3,5 receptor
IP3 + DAG) conductance from α1 adrenoreceptor
ER
DAG  PKC
Other 2nd messenger systems (not part of question)
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

cGMP linked NO Guanylyl cyclase  (GTP cGMP  ↑ light NO receptor

 cGMP) chain phosphatase
Tyrosine Insulin, EGF, Dimerization 
Kinase PDGF phosphorylation
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

Physiol-01B5/97A1/93A2 Describe the structure and function of voltage gated ion channels. How are
they investigated? Describe one commonly interfered with in Anaesthesia.

1. Ion channels are proteins that traverse the lipid bilayer cell membrane, which contain a
hydrophobic core to allow the diffusion of ions down their concentration gradient across the
membrane.

2. Types
a. Non-gated: porins and gap junctions
b. Gated:
i. Voltage gated – Na, K, Ca
ii. Ligand gated – Nicotinic ACh, GABA
iii. G-protein coupled – adrenoreceptors, muscurinic receptors
iv. Stress gated

3. Voltage sensitive ion channels are transmembrane ion channels which control the passive
diffusion of ions down the concentration gradient across cell membranes, through their
response to changes in membrane potential. The most important voltage gated channels are the
a. Na, K in nerve and muscle membrane
b. Ca channels in presynaptic nerve endings

4. Structure:
a. Multiple subunits –most channels consist of 4 subunits. Each subunit consists of 6
homologous membrane spanning α-helices. These subunits are responsible for various
properties including ion selectivity, sensor for voltage, and conformation change to
open/close the channel.
b. 4th α-helix is the most important functional component. It has positive charged amino
acid chain and contains the voltage sensor which changes position depending in the
potential – ‘gating’.
c. Central pore – the pore is an opening enclosed by the subunits. It is selective to
particular ions by virtue of the transmembrane helices which surround it.
d. States of the ion channel:
i. Open – ion flows across membrane
ii. Closed – no ion flow. Concentration gradient maintained.
iii. Inactive – state of closure where the channel cannot be open again. This
accounts for the refractory period.

5. Types and function of VGIC

Channel Na K Ca
Location Nerve cells Cardiac myocytes 3 types: N, L and T
Muscle cells Nerve cells (delayed L type: cardiac myocytes
rectifier) (phase II)
Presynaptic nerve
terminals
Function AP transmission across Repolarisation of cell Cardiac DP
membrane membrane following Automaticity of pacemaker
depolarisation cells
Exocytosis of
neurotransmitters.
Activation RMP > -65mV (threshold) ↓RMP of sarcolemma RMP > -40mV (threshold)
Effect of opening Fast influx Na Slow efflux K Slow Ca influx
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

Depolarisation Repolarisation Depolarisation

Also : Li (1), K (1/12), Also: thallium, rubidium,
rubidium (1/40) ammonium
Antagonists Tetrodotoxin, Saxitoxin Caesium, barium, Verapamil,
↓pH strychnine, quinidine. Dihydropyridines, divalent
LAs (cytosolic binding site) cations (Mn, Ni, Co).
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

Physiol-98B7 Briefly describe structure of mitochondria. Outline the metabolic processes that occur in
mitochondria 64%

1. Mitochondria are energy producing organelles within all cells over the body (except mature
RBCs). They are necessary for the production of ATP and the number of mitochondria in each
cell is proportionate to the metabolic activity.

2. Structure: rod shaped structure which lies within the cytoplasm, with an outer and inner
membrane.
a. Inner membrane: multiple folds (cristae) which make up the matrix. This contains large
quantities of enzymes important in energy cycles (Krebs, oxidative phosphorylation).
b. Outer membrane: contains enzymes important in providing substrates for the inner
mitochondrial energy cycles. E.g. MAO.
c. Intracristal space: the space outside the inner membrane which contains high
concentrations of H+ for oxidative phosphorylation.
d. DNA: the mitochondria has the ability to synthesise its own mRNA and proteins. Hence it
can replicate its own DNA and divide according to energy needs of the cell.
Mitochondrial DNA is derived exclusively from the maternal ovum during fertilisation.

3. Metabolic processes: producing ATP by aerobic metabolism from fuel sources of carbohydrates,
fats and proteins through the Krebs cycle and oxidative phosphorylation.
a. Breakdown of fuels – the 3 basic fuels are broken down into a common product 
Acetyl CoA
i. Carbohydrate: glucose converted into pyruvate (in cytoplasm), where is enters
the mitochondrial matrix to be oxidised to acetyl CoA.
ii. Lipids: β-oxidation in the cytoplasm strips 2 carbons off the fatty acid  acetyl
CoA.
iii. Proteins: amino acids undergo glucogenic transamination  pyruvate which
diffuses into the matrix to become oxidised to Acetyl CoA.
b. Krebs cycle
i. Occurs in the mitochondrial matrix
ii. Acetyl CoA enters the cycle and generates CO2 + H atoms with electrons which
are carried by the reduction of intermediaries NAD  NADH, FADH  FADH2.
c. Oxidative phosphorylation – using the electrons from H-atoms to generate a driving
gradient for ATP synthesis.
i. NADH and FADH2 travel to the inner membrane and release H
ii. The membrane contains the electron transport chain – a series of enzymes
which catalyse oxidation of NADH, FADH.
iii. Splitting H  H+ + e-
iv. 4e- + 4H+ + O2  2H2O (ETC enzymes)
v. Energy released by electron transport is used to pump H+ from matrix 
intracristal space (sets up concentration gradient).
vi. Energy released by flow of H+ down gradient through ATP synthetase which
catalyses ADP  ATP. 3 ATP molecules for every 2e- transported.
 Dr Matthew Ho
BSc(Med) MBBS(Hons) FANZCA

Physiol-91 Write short notes on the Endoplasmic Reticulum

1. The endoplasmic reticulum is a group of organelles within the cell’s cytosol which have a lipid
bilayer membrane and are important in the synthesis of enzymes and lipids necessary for cell
function.

2. It consists of 3 parts:
a. Rough endoplasmic reticulum: contains ribosomes on the membrane surface for protein
synthesis. mRNA (produced from DNA transcription) undergoes translation at ribosomal
binding sites. tRNA brings amino acids to incorporate on to the polypeptide chain.
Products are released into the Golgi apparatus for further processing.
b. Smooth endoplasmic reticulum: devoid of ribosomes, this contains enzymes responsible
for gluconeogenesis, lipid synthesis and functionalisation (phase I reactions).
c. Sarcoplasmic reticulum: a special type of smooth ER which acts as a calcium store in
cardiac and smooth muscle myocytes.