CNS channelopathies 1

Question 1

What is ataxia

Answer 1

Uncontrolled muscle contraction

Question 2

What are triggers for both type 1 and type II episodic ataxias

Answer 2

Physical/ emotional stress - sudden changes in position

Question 3

What are some common symptoms of both type I and type II ataxias

Answer 3

Ataxia, dizziness, vertigo, visual blurring

Question 4

What is the cause of type I ataxia

Answer 4

Brief shaking attacks - KCNA1 gene mutation
Channel is found in the cerebellum and at neuromuscular junctions - Loss of function mutations scattered throughout subunits of the channel

Question 5

How does a mutation in KCNA1 cause ataxia

Answer 5

K channel usually mediates repolarization so neurons become excited for longer inappropriately

Question 6

What is a treatment for episodic type I ataxia

Answer 6

Acetazolamide - carbonic anhydrase inhibitor - changes body fluid pH dampening the excitability of neurons

Question 7

What is the mutation that causes episodic type II ataxia

Answer 7

30min->24hr shaking attacks
P/Q type Calcium channel CaCNA1A mutation found in the cerebellum
Many point mutations and mostly truncation mutations

Question 8

What is the structure of the P/Q type calcium channel

Answer 8

24 TMDs - 4 sets of 6 which each form a pore subunit

Question 9

Where is CACNA1A found

Answer 9

In purkinje cells and granule cells of the cell bodies of central neurons - Calcium firing acts as a signal for neurotransmission by exocytosis
Less firing due to a reduction in calcium - less ability to co-ordinate movements - normal cerebellar function

Question 10

What does the G293R mutation cause

Answer 10

calcium flow is reduced
Caused by a change in voltage dependence
Calcium gets max flow at +10mV instead of 0
Means they take longer to open and are open for a shorter amount of time
Less Ca means less neurotransmitter release
Problems with skeletal muscle control