MSK Individual Readiness Assurance Test (iRAT) Practice Test

A mutation in the SCN4A gene leading to HYPP affects which voltage-gated ion channel?

Sodium channel Potassium channel Calcium channel Chloride channel

Correct Answer:

Sodium channel

Explanation:

HYPP from SCN4A mutations alters the skeletal muscle voltage-gated sodium channel (Nav1.4). The SCN4A gene encodes the alpha subunit that gates sodium influx necessary for action potential initiation. Mutations often cause a gain-of-function effect—abnormal persistent sodium current or delayed inactivation—leading to abnormal depolarization of muscle fibers. When serum potassium rises, the depolarized state reduces excitability and produces episodic weakness or paralysis. Since SCN4A encodes a sodium channel, the primary channel affected is the sodium channel; potassium, calcium, and chloride channels are not the direct targets of this mutation.

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