Characterization of the cardiac sodium channel SCN5A mutation, N1325S, in single murine ventricular myocytes

Sandro L. Yong, Ying Ni, Teng Zhang, David J. Tester, Michael John Ackerman, Qing K. Wang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The N1325S mutation in the cardiac sodium channel gene SCN5A causes the type-3 long-QT syndrome but the arrhythmogenic trigger associated with N1325S has not been characterized. In this study, we investigated the triggers for cardiac events in the expanded N1325S family. Among 11 symptomatic patients with document triggers, six died suddenly during sleep or while sitting (bradycardia-induced trigger), three died suddenly, and two developed syncope due to stress and excitement (non-bradycardia-induced). Patch-clamping studies revealed that the late sodium current (INa,L) generated by mutation N1325S in ventricular myocytes from TG-NS/LQT3 mice was reduced with increased pacing, which explains bradycardia-induced mortalities in the family. The non-bradycardic triggers are related to the finding that APD became prolonged and unstable at increasing rates, often with alternating repolarization phases which was corrected with verapamil. This implies that Ca2+ influx and intracellular Ca2+ ([Ca2+]i) ions are involved and that [Ca2+]i inhomogeneity may be the underlying mechanisms behind non-bradycardia LQT3 arrhythmogenesis associated with mutation N1325S.

Original languageEnglish (US)
Pages (from-to)378-383
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume352
Issue number2
DOIs
StatePublished - Jan 12 2007

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pamidronate
Sodium Channels
Verapamil
Muscle Cells
Genes
Sodium
Ions
Bradycardia
Mutation
Syncope
Constriction
Sleep
Mortality

Keywords

  • APD
  • Intracellular Ca
  • Late persistent sodium current
  • Sodium channel gene SCN5A
  • Sudden death
  • Type 3 long-QT syndrome (LQTS)
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Characterization of the cardiac sodium channel SCN5A mutation, N1325S, in single murine ventricular myocytes. / Yong, Sandro L.; Ni, Ying; Zhang, Teng; Tester, David J.; Ackerman, Michael John; Wang, Qing K.

In: Biochemical and Biophysical Research Communications, Vol. 352, No. 2, 12.01.2007, p. 378-383.

Research output: Contribution to journalArticle

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