Role of Sodium Channels in Propagation in Heart Muscle: How Subtle Genetic Alterations Result in Major Arrhythmic Disorders

Authors


  • This study was supported in part by an NIM grant (ROI ML56810-9) received by Dr. Kass.

  • Manuscript received 19 September 2006; Revised manuscript received 27 February 2007; Accepted for publication 14 March 2007.

  • Editor: Augustus O. Grant, M.D.

Address for correspondence: C. Terrenoire, Ph.D., Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 W. 168th St. P&S 7-401, New York, NY 10032. Fax: 212-305-8780; E-mail: ct2068@columbia.edu

Abstract

Sodium channels play a crucial role in initiation, propagation, and maintenance of cardiac excitation throughout the heart. Indeed, dysfunctional sodium channels have been shown to be responsible for several inherited cardiac electrical disorders, such as Long QT and Brugada syndromes (BrS), potentially leading to fatal arrhythmic events. Genetic approaches and functional experiments using heterologous systems have enabled the characterization of the molecular determinants involved in these disorders and their consequences on ion channel function. The improved understanding of the mechanisms leading to these cardiac arrhythmic events represents a first step in the development of therapeutic treatments.

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