Paramyotonia congenita and skeletal sodium channelopathy.

Paramyotonia congenita, the major characteristics of which are cold-induced and exercise-induced myotonia, is an autosomal-dominant muscle disease which is classified into one of a group of muscle diseases, so-called muscle "sodium channelopathies" caused by missense mutations in the gene coding for the skeletal muscle sodium channel a-subunit (SCN4A) (1-4). Such muscle sodium channelopathies share a commonabnormality of muscle membraneexcitability, which could be expressed as myotonia or weakness. These channelopathies include three allelic disorders, namely paramyotonia congenita, hyperkalemic periodic paralysis and sodium channel myotonias (1-3, 5). These mutations of the skeletal muscle sodium channel causing sodium channelopathies all exhibit gain-of-function defects. The pathophysiology of sodium channelopathies is currently considered as follows. In the sodium channel-