Lecture 7 - Ion channels and properties

Question 1

Ion channels: what are they, what do they do, what is the pore, and how many subunits do they have?

Answer 1

A transmembrane protein that forms a selective gated pore which allows ions to passively cross a membrane

Their transmembrane pore enables charged particles to move across the membrane

The pore is the simplest and main functional component of an ion channel

Multimeric

Question 2

How is ion channel movement facilitated?

Answer 2

The electrochemical gradient - a combination of a concentration and electric field gradient - determines the direction that ions will flow through an open channel pore

Question 3

Na-channel inhibitors: what do they do?

Answer 3

Anti-arrhythmic drugs, local anaesthetics

Question 4

K-channel inhibitors: what do they do?

Answer 4

Diabetes therapy

Question 5

K-channel openers: what do they do?

Answer 5

Antihypertensive, angina, hyperinsulism, etc

Question 6

HERG K-channel: what does it do?

Answer 6

Drug toxicology screening

Question 7

Toxins affecting ion channels: what are the examples, what do they target, and what do they do?

Answer 7

Conotoxin (snail(?)), chlorotoxin (scorpion), apamin (bee/wasp?), tetrodotoxin (pufferfish), ciguatoxin (plant), brevetoxin (plant), etc

Target a variety of ion channels (potassium, calcium, sodium and chloride channels)

These molecules are often highly potent, selective and, sometimes, have a potential
therapeutic value depending on their cellular targets

Question 8

What types of gating are there?

Answer 8

• Chemically/ligand-gated - permeability increased by a ligand binding
• Voltage-gated - permeability changes in response to membrane voltage
• Mechanically-gated - permeability changes in response to mechanical membrane forces such as tension

Question 9

Nernst potential/equation: what are they and what do they do?

Answer 9

Nersnt potential - the net flow of ions in equilibrium

Nersnt equation - used to predict the systems of one permeant ion species

Question 10

Goldman-Hodgin-Katz equation

Answer 10

Used to predict the systems of more than one permeant ion species

Eₘ = RT/F (Pₙₐ(Na⁺)ₒ/Pₙₐ(Na⁺)ᵢ+….)

Eₘ - membrane potential (V)
R - Gas constant (8.31(?))
T - Kelvin
F - Faraday’s constant (?)
Pₓ - ion selectivity
(X)ₒ - extracellular ion concentration
(X)ᵢ - intracellular ion concentration

Question 11

What causes membrane resting potential?

Answer 11

The ionic species that has the greatest permeability across the membrane

Question 12

What do K-channel activators/inhibitors and Na-channel activators do?

Answer 12

K-channel inhibitors - depolarisation
Activators - repolarisation/hyperpolarisation

Na-channel activators - depolarisation

Question 13

Action potentials

Answer 13

2-3ms process:
* Resting membrane potential reaches threshold potential (-55mV)
* Ca²⁺/Na⁺ channels open and K⁺ channels close - depolarisation
* Transition period - Ca²⁺/Na⁺ channels inactivated, K⁺ channels open
* Repolarisation - Ca²⁺/Na⁺ channels close, K+ channels open
Hyperpolarisation - K⁺ channels open
Refractory period - K⁺ channels close, resting membrane potential is back to normal

Occurs mainly in skeletal, nerve, and endocrine

Question 14

Cardiac myocyte

Answer 14

Similar to action potential but with a much slower rate (~1000ms), with a very rapid depolarisation stage and a much slower repolarisation stage