CNS channelopathies 2

Question 1

What is the fundamental causes of epilepsy

Answer 1

Too much activity in excitatory neurons due to changes in ion channels - fire too many APs
Too little activity of inhibitory neurons which aren’t working well - no dampening of excitation

Question 2

What is the role of Nav channels

Answer 2

Depolarization in both excitatory and inhibitory neurons

Question 3

What is the role of K channels

Answer 3

Repolarization in both excitatory and inhibitory neurons

Question 4

What is the role of Ca in neuronal ion channels

Answer 4

Evokes the release of neurotransmitters

Question 5

What is the role of AchR in neuronal ion channels

Answer 5

Post synaptic membrane excitation

Question 6

What is the role of GABAa receptors in neuronal ion channels

Answer 6

Post synaptic membrane inhibition

Question 7

What is the role of HCN in neuronal ion channels

Answer 7

Hyperpolarization - activated cyclic nucleotide gated channel - open probability goes up as the membrane potential hyperpolarizes - leading to depolarization - important in determining how many APs are fired per unit time

Question 8

How does a P/Q type Ca channel mutation cause epilepsy

Answer 8

No neurotransmitter release at the inhibitory presynapse

No GABA release so no Cl influx - no hyperpolarization of excitatory neuron so they become over excitatory

Question 9

How does a Nav1.1 channel mutation cause epilepsy

Answer 9

Nav1.1 found in the inhibitory neuron - mediates depolarization of the axon to fire AP - intracellular calcium remains low - less GABA release - less inhibition

Question 10

What mutations are seen in the Nav1.1 channel

Answer 10

either missense or truncation - scattered throughout the protein

Question 11

What is the mutation seen in AchR and where are they found

Answer 11

Gain of function mutation - found on the post synaptic membrane of the excitatory neurons

Question 12

What is the mutation in the Nav1.2 channel and where are the channels found

Answer 12

Gain of function - found on the excitatory axons

Question 13

What is the mutation in the HCN channel and where are the channels found

Answer 13

Loss of function mutation - Found on the excitatory dendrites - Increases excitability due to loss of firing control

Question 14

What is the mutation in the Kv7.2 channel and where are the channels found

Answer 14

Loss of function - found on the excitatory axon - Increase in excitability due to loss of firing control

Question 15

How does Nav1.7 channel mutations lead to pain disorders

Answer 15

Found in peripheral sensory neurons

Mutations cause lack/gain of pain depending on if it is a loss or gain of function mutation