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

14 Citations (Scopus)

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

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Paralysis
Hyperkalemic Periodic Paralysis
Myotonic Disorders
Mutation
Skeletal Muscle
Phenotype
Syndrome
Potassium aggravated myotonia
Recovery
Elevation
Fold
Cells
Causes

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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

Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome. / Lossin, Christoph; Nam, Tai Seung; Shahangian, Shahab; Rogawski, Michael A; Choi, Seok Yong; Kim, Myeong Kyu; Sunwoo, Il Nam.

In: Neurology, Vol. 79, No. 10, 04.09.2012, p. 1033-1040.

Research output: Contribution to journalArticle

Lossin, C, Nam, TS, Shahangian, S, Rogawski, MA, Choi, SY, Kim, MK & Sunwoo, IN 2012, 'Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome', Neurology, vol. 79, no. 10, pp. 1033-1040. https://doi.org/10.1212/WNL.0b013e3182684683
Lossin, Christoph ; Nam, Tai Seung ; Shahangian, Shahab ; Rogawski, Michael A ; Choi, Seok Yong ; Kim, Myeong Kyu ; Sunwoo, Il Nam. / Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome. In: Neurology. 2012 ; Vol. 79, No. 10. pp. 1033-1040.
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AU - Sunwoo, Il Nam

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