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Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia

2011; Lippincott Williams & Wilkins; Volume: 76; Issue: 19 Linguagem: Inglês

10.1212/wnl.0b013e318219fb57

1526-632X

David Francis, Volodymyr Rybalchenko, Arie Struyk, Stephen C. Cannon,

Planarian Biology and Electrostimulation

Background: Hypokalemic periodic paralysis (HypoPP) is associated with mutations in either the Ca V 1.1 calcium channel or the Na V 1.4 sodium channel. Some Na V 1.4 HypoPP mutations have been shown to cause an anomalous inward current that may contribute to the attacks of paralysis. Herein, we test whether disease-associated Na V 1.4 mutations in previously untested homologous regions of the channel also give rise to the anomalous current. Methods: The functional properties of mutant Na V 1.4 channels were studied with voltage-clamp techniques in an oocyte expression system. Results: The HypoPP mutation Na V 1.4-R1132Q conducts an anomalous gating pore current, but the homologous R1448C mutation in paramyotonia congenita does not. Conclusions: Gating pore currents arising from missense mutations at arginine residues in the voltage sensor domains of Na V 1.4 are a common feature of HypoPP mutant channels and contribute to the attacks of paralysis.