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Voltage‐sensor mutations in channelopathies of skeletal muscle
Author(s) -
Can Stephen C.
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.186874
Subject(s) - myotonia , periodic paralysis , depolarization , hypokalemic periodic paralysis , gating , sodium channel , channelopathy , paralysis , skeletal muscle , neuroscience , biophysics , chemistry , biology , endocrinology , genetics , medicine , myotonic dystrophy , sodium , hypokalemia , surgery , organic chemistry
Mutations of voltage‐gated ion channels cause several channelopathies of skeletal muscle, which present clinically with myotonia, periodic paralysis, or a combination of both. Expression studies have revealed both loss‐of‐function and gain‐of‐function defects for the currents passed by mutant channels. In many cases, these functional changes could be mechanistically linked to the defects of fibre excitability underlying myotonia or periodic paralysis. One remaining enigma was the basis for depolarization‐induced weakness in hypokalaemic periodic paralysis (HypoPP) arising from mutations in either sodium or calcium channels. Curiously, 14 of 15 HypoPP mutations are at arginines in S4 voltage sensors, and recent observations show that these substitutions support an alternative pathway for ion conduction, the gating pore, that may be the source of the aberrant depolarization during an attack of paralysis.