NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery.

ABSTRACT: Hypokalaemic periodic paralysis is typically associated with mutations of voltage sensor residues in calcium or sodium channels of skeletal muscle. To date, causative sodium channel mutations have been studied only for the two outermost arginine residues in S4 voltage sensor segments of domains I to III. These mutations produce depolarization of skeletal muscle fibres in response to reduced extracellular potassium, owing to an inward cation-selective gating pore current activated by hyperpolarization. Here, we describe mutations of the third arginine, R3, in the domain III voltage sensor i.e. an R1135H mutation which was found in two patients in separate families and a novel R1135C mutation identified in a third patient in another family. Muscle fibres from a patient harbouring the R1135H

SUBMITTER: Groome JR 

PROVIDER: S-EPMC3959555 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature