Referenced in: none

Automatically associated channels: Nav1.4 , Slo1

Title: Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome.

Authors: Christoph Lossin, Tai-Seung Nam, Shahab Shahangian, Michael A Rogawski, Seok-Yong Choi, Myeong-Kyu Kim, Il-Nam Sunwoo

Journal, date & volume: Neurology, 2012 Sep 4 , 79, 1033-40

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22914841

Abstract
To electrophysiologically characterize the Na(v)1.4 mutant N440K found in a Korean family with a syndrome combining symptoms of paramyotonia congenita, hyperkalemic periodic paralysis, and potassium-aggravated myotonia.We characterized transiently expressed wild-type and mutant Na(v)1.4 using whole-cell voltage-clamp analysis.N440K produced a significant depolarizing shift in the voltage dependence of fast inactivation and increased persistent current and acceleration in fast inactivation recovery, which gave rise to a 2-fold elevation in the dynamic availability of the mutant channels. In addition, the mutant channels required substantially longer and stronger depolarization to enter the slow-inactivated state.N440K causes a gain of function consistent with skeletal muscle hyperexcitability as observed in individuals with the mutation. How the same mutation results in distinct phenotypes in the 2 kindreds remains to be determined.