Hypokalemic periodic paralysis: An autosomal dominant muscle disorder caused by mutations in a voltage-gated calcium channel

Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder characterized by acute attacks of muscle weakness concomitant to a drop in blood potassium levels. Recent molecular work has shown that hypoPP is due to mutations in a skeletal muscle voltage-gated calcium channel: the dihydropyridine receptor (DHP receptor). Mutations affect segments S4 of domains II and TV, changing an arginine in position 528 and 1239 into an histidine, or an histidine or a glycine respectively, Surprisingly, expressing in vitro mutants channels in a non-muscular environnement resulted in functional calcium channels with minor modifications in electrophysiological properties. Expressing mutant channels in a muscular environnement or transgenic mice might help to bridge the gap between the knowledge of the molecular defect and the understanding of the pathophysiology of the disease. (C) 1997 Elsevier Science B.V.