CNS channelopathies Flashcards
What is the occurrence of episodic ataxia?
1:100000
What is type 1 episodic ataxia caused by?
KCNA1 (Kv) dominant mutation
What is the onset of type 1 episodic ataxia?
10-20years
What is type 2 episodic ataxia caused by?
Autosomal dominant mutation in CACNA1a
What is the onset of type 2 ataxia?
Child to teens
What is the trigger for type 1 episodic ataxia?
Physical/ emotional stress, vestibular system, abrupt change position
What are symptoms of type 1 episodic ataxia?
Ataxia, dizziness and visual blurring
What does KCNA1 mutant do?
Much reduced current, loss of function mutation which results in increased excitability of the cell as cell has lower repolarisation
What are treatments for type 1 episodic ataxia?
Acetazolamide- Carbonic anhydrase inhibitor which changes bicarbonate handling in kidney which dampens cerebellum
Phenytoin- Sodium channel blocker
Carbamazepine- Sodium channel blocker
What is the trigger for type 2 episodic ataxia?
Physical and emotional stress
What are the symptoms of Type 2 episodic ataxia?
Ataxia, trunk instability, nystagmus, vertigo, nausea, vomitting, headache
Where is KCNA1?
In NMJs and cerebellum
Where is CACNA1A?
Cerebellum
What is the structure of CACNA1A?
24 trans, 4 voltage sensory, 4 pore regions, P/Q type calcium channel
What happens with CACNA1A mutant?
Not enough NT release. Opens later (at high Vm, and less current through)
What is treatment for type 2?
Acetazolamide
What is the occurrence of epilepsy?
0.5-1%
What is HCN?
Hyperpolarisation-activated cyclic nucleotide gated channel for depolarisation
What mutations can Nav1.1 have?
Missense or truncation - determine type of epilepsy
What is Nav1.1 for?
AP firing in inhibitory neuron
What does KO Nav1.1 mice show?
Ability of neutrons in mutant to fire AP is reduced so less activation of GABAaR on post so post moves closer to threshold so can fire more APs
What is the location of GABAaR?
Post synaptic membrane of excitiatory neuron
Where is AChR?
Post synaptic membrane of excitatory neurons
What is the location of Nav1.2?
Excitatory neurons
What does Kv7.2 do?
Changes the resting Vm so increase the firing rate
What do mutations in HCN and Kv7.2 do?
Increase in firing rate of AP
