Multiple mechanisms of Na+ channel-linked long-QT syndrome

Robert Dumaine, Qing Wang, Mark T. Keating, Hali A. Hartmann, Peter J. Schwartz, Arthur M. Brown, Glenn E. Kirsch

Research output: Contribution to journalArticlepeer-review


Inheritable log-QT syndrome (LQTS) is the disease in which delayed ventricular repolarization leads to cardiac arrhythmias and the possibility of sudden death. In the chromosome 3-linked disease, one mutation of the cardiac Na+ channel gene result in substitutions (N1325S and R1644H). We compared all three mutant-channel pheno types by heterologous expression in Xenopus oocytes. Each produced a late phase of inactivation-resistant- channel pheno-types by heterologous expression in Xenopus oocytes. Each produced a late phase of inactivation-resistant, but the underlying mechanisms were different at the single-channel level. N1325S and R1644H showed dispersed reopenings after the initial transient, whereas δKPQ showed both dispersed reopenings and long-lasting bursts. Thus, two distinct biophysical defects underlie the in vitro penotype of persistent current in Na+ channel-linked LQTS, and the additive effects of both are responsible for making the δKPQ phenotype the most severe.

Original languageEnglish
Pages (from-to)916-924
Number of pages9
JournalCirculation Research
Issue number5
Publication statusPublished - May 1996


  • cardiac arrhythmia
  • human heart
  • Na± channels
  • Romano-Ward syndrome
  • site-directed mutagenesis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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