TY - JOUR
T1 - Voltage-sensor mutations in channelopathies of skeletal muscle
AU - Cannon, Stephen C.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
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U2 - 10.1113/jphysiol.2010.186874
DO - 10.1113/jphysiol.2010.186874
M3 - Review article
C2 - 20156847
AN - SCOPUS:77954460669
SN - 0022-3751
VL - 588
SP - 1887
EP - 1895
JO - Journal of Physiology
JF - Journal of Physiology
IS - 11
ER -