Inherited erythermalgia moves a sodium channel into focus

Abstract

Voltage-gated sodium channels generate the all-or-nothing action potentials that are the defining characteristic of excitable cells. The first mutation in a human sodium channel gene, found in the skeletal muscle sodium channel gene SCN4A , and causing hyperkalemic periodic paralysis, was described in 1991.1 This mutation has turned out to be the tip of an iceberg. Of the nine genes encoding voltage-gated sodium channels, hundreds of mutations spread among six genes have now been associated with a variety of inherited, mostly episodic diseases in humans.2,3 The close conservation of sodium channels which, unlike calcium and potassium channels, are all members of a single family,4 means that very few compounds distinguish between the members of the family. Consequently, while it is clear they are differentially localized within cells and tissues, pharmacologically teasing apart the functions of different sodium channel subtypes in vitro is impossible in many cases.5 The lack of pharmacologic tools, combined with the emergence of discrete sodium channelopathies, means that the functional roles of different sodium channel subtypes …