Ion Channels

Question 1

What ion primarily controls membrane potential and what ensures passive ion transport doesn’t right the balance?

Answer 1

K and the Na/K-ATPase pump

Question 2

What is the undershoot of an AP?

Answer 2

A transient period of hyperpolarisation that acts as a post-AP refractory period.

Question 3

What activates a mechanically-gated ion channel?

Answer 3

Membrane stretch

Question 4

Intro to voltage-gated ion channels

Answer 4

Proteins that form pores for ions to flow though at a fast rate
Opening is voltage-dependent and ions flow according to electrochemical gradients

Question 5

What is the S4 family of channels?

Answer 5

All built with 6 segments, segment 4 is the voltage sensor that induces a conformational change. S5-6 are responsible for ion selectivity.
Auxiliary subunits also present

Question 6

What is the function of auxiliary subunits?

Answer 6

Modulate gating, kinetics, intracellular trafficking and current amplitude

Question 7

Structure and function of Kv channels

Answer 7

Tetramer of identical 4v-alpha subunits + auxiliary units
Terminates the AP (repolarisation) by letting K through
? therapeutic targets for increased APs ie. epilepsy

Question 8

Structure and function of Cav channels

Answer 8

1x Cav-alpha1 subunit with 3x auxiliary units, classified based on Cava1 subtype
Important for NT release, synaptic plasticity and pain
N-type channel blockers are analgesics

Question 9

Structure and function of Nav channels

Answer 9

One Nav-alpha unit with an auxiliary Nav-beta unit. Has an inactivation gate, open when resting but closed when the channel is repolarising and inactivated.
Does the rising phase of the AP :. very important for pain pathways

Question 10

What is the mechanism of lidocaine?

Answer 10

Binds to inside of Nav channel so AP cannot progress (tetrodotoxins work this way too but permanently in CNS/PNS)

Question 11

Structure/function of Clv channels

Answer 11

Dimers, open individually or together.

Question 12

What does it take to open an ionotropic receptor?

Answer 12

Usually more than 1 NT molecule as they’re multimeric

Question 13

What is a seizure?

Answer 13

Clinical manifestation of abnormal, excessive hypersynchronous discharge of a population of cortical neurons.

Question 14

Seizure initiation

Answer 14

AP burst AKA paroxysmal depolarising shift causes abnormal and excessive synchronisation of neighbouring populations of cortical cells

Question 15

Seizure propagation

Answer 15

Activation of nearby neurons and loss of surrounding inhibition causes spread of the partial seizure

Question 16

How do over-excitation and under-inhibition cause seizures?

Answer 16

Excitation ++ leads to sustained depolarisation, mediated by glutamate
Inhibition – causes hyperpolarisation defects, mediated by GABA

Question 17

What are the main targets of anti-epileptic drugs?

Answer 17

1. Voltage-gated Na and Ca channels to inhibit high-frequency spike firing
2. GABAa receptors as they promote hyperpolarisation and prevent AP propagation
3. Others, including NMDA antagonists to prevent excitation and Kv channel activators

Question 18

Mechanism of action of lamotrigine?

Answer 18

Selectively blocks high-frequency repetitive spoke firing during seizure spread without affecting normal activity (maybe also some Cav activity)

Question 19

What channels are targeted by anti-epileptic drugs?

Answer 19

Na/Ca voltage mainly, GABA and glutamate to a lesser degree