Altered fast and slow inactivation of the N440K Na(v)1.4 mutant in a periodic paralysis syndrome

作者：Lossin Christoph; Nam Tai Seung; Shahangian Shahab; Rogawski Michael A; Choi Seok Yong; Kim Myeong Kyu^*; Sunwoo Il Nam

来源：Neurology, 2012, 79(10): 1033-1040.

DOI：10.1212/WNL.0b013e3182684683

Objective: 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. %26lt;br%26gt;Methods: We characterized transiently expressed wild-type and mutant Na(v)1.4 using whole-cell voltage-clamp analysis. %26lt;br%26gt;Results: 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. %26lt;br%26gt;Conclusions: 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. Neurology (R) 2012;79:1033-1040

• 出版日期2012-9