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

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

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective: To electrophysiologically characterize the Nav1.4 mutant N440K found in a Korean family with a syndrome combining symptoms of paramyotonia congenita, hyperkalemic periodic paralysis, and potassium-aggravated myotonia. Methods: We characterized transiently expressed wild-type and mutant Nav1.4 using whole-cell voltage-clamp analysis. 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. 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.

Original languageEnglish (US)
Pages (from-to)1033-1040
Number of pages8
JournalNeurology
Volume79
Issue number10
DOIs
StatePublished - Sep 4 2012

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Fingerprint Dive into the research topics of 'Altered fast and slow inactivation of the N440K Na<sub>v</sub>1.4 mutant in a periodic paralysis syndrome'. Together they form a unique fingerprint.

  • Cite this

    Lossin, C., Nam, T. S., Shahangian, S., Rogawski, M. A., Choi, S. Y., Kim, M. K., & Sunwoo, I. N. (2012). Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome. Neurology, 79(10), 1033-1040. https://doi.org/10.1212/WNL.0b013e3182684683