A sodium channel defect in hyperkalemic periodic paralysis: Potassium-induced failure of inactivation

Stephen C. Cannon, Robert H. Brown Jr., David P. Corey

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

Hyperkalemic periodic analysis (HPP) is an autosomal dominant disorder characterized by episodic weakness lasting minutes to days in association with a mild elevation in serum K+. In vitro measurements of whole-cell currents in HPP muscle have demonstrated a persistent, tetrodotoxin-sensitive Na+ current, and we have recently shown by linkage analysis that the Na+ channel α subunit gene may contain the HPP mutation. In this study, we have made patch-clamp recordings from cultured HPP myotubes and found a defect in the normal voltage-dependent inactivation of Na+ channels. Moderate elevation of extracellular K+ favors an aberrant gating mode in a small fraction of the channels that is characterized by persistent reopenings and prolonged dwell times in the open state. The Na+ current, through noninactivating channels, may cause the skeletal muscle weakness in HPP by depolarizing the cell, thereby inactivating normal Na+ channels, which are then unable to generate an action potential. Thus the dominant expression of HPP is manifest by inactivation of the wild-type Na+ channel through the influence of the mutant gene product on membrane voltage.

Original languageEnglish (US)
Pages (from-to)619-626
Number of pages8
JournalNeuron
Volume6
Issue number4
DOIs
StatePublished - Apr 1991

ASJC Scopus subject areas

  • Neuroscience(all)

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