A combined approach using patch-clamp study and computer simulation study for understanding long QT syndrome and TdP in women

Tetsushi Furukawa, Junko Kurokawa, Colleen E Clancy

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Female sex is an independent risk factor for development of torsade de pointes (TdP)-type arrhythmias in both congenital and acquired long QT syndrome (LQTS). In females, QTc interval and TdP risk vary during the menstrual cycle and around delivery. Biological experiments including single-cell current recordings with the patch-clamp technique and biochemical experiments show that progesterone modulates cardiac K+ current and Ca2+ current via the non-genomic pathway of the progesterone receptor, and thus the cardiac repolarization duration, in a concentration-dependent manner. Incorporation of these biological findings into a computer model of single-cell and coupled-cell cardiomyocytes simulates fluctuations in QTc interval during the menstrual cycle with reasonable accuracy. Based on this model, progesterone is predicted to have protective effects against sympathetic nervous system-induced arrhythmias in congenital LQTS and drug-induced TdP in acquired LQTS. A combined biological and computational approach may provide a powerful means to risk stratify TdP risk in women.

Original languageEnglish (US)
Pages (from-to)244-250
Number of pages7
JournalCurrent Cardiology Reviews
Volume4
Issue number4
DOIs
StatePublished - 2008
Externally publishedYes

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Keywords

  • Arrhythmia
  • Long QT syndrome
  • Nitric oxide
  • Non-genomic pathway
  • Patch-clamp
  • Sex hormone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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