From mutation to myotonia in sodium channel disorders

Abstract

Hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium-aggravated myotonias are all caused by point mutations in the alpha-subunit of a sodium channel expressed selectively in skeletal muscle. This review updates the growing list of genotype-phenotype correlations for these mutations and summarizes the alterations in channel function they produce. A toxin-based in vitro model demonstrates that subtle defects in sodium channel inactivation are sufficient to cause myotonia and computer modeling suggests that specific types of inactivation defect may predispose to paralysis or myotonia.