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

被引:43
作者
Francis, David G. [3 ]
Rybalchenko, Volodymyr [4 ]
Struyk, Arie [5 ]
Cannon, Stephen C. [1 ,2 ]
机构
[1] UT SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA
[2] UT SW Med Ctr, Program Neurosci, Dallas, TX 75390 USA
[3] UT SW Med Ctr, Dept Anesthesiol, Dallas, TX 75390 USA
[4] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA
[5] Merck Res Labs, N Wales, PA USA
关键词
GATING PORE CURRENT; SKELETAL-MUSCLE; DEPOLARIZATION; K+; CHANNELOPATHIES; INACTIVATION; TYPE-2; BRAIN; SCN4A;
D O I
10.1212/WNL.0b013e318219fb57
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 onducts 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. Neurology (R) 2011; 76: 1635-1641
引用
收藏
页码:1635 / 1641
页数:7
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