The cardiac sodium channel: gating function and molecular pharmacology

J Mol Cell Cardiol. 2001 Apr;33(4):599-613. doi: 10.1006/jmcc.2000.1346.


Cardiac sodium (Na) channels are dynamic molecules that undergo rapid structural changes in response to the changing electrical field in the myocardium. Inherited mutations in SCN5A, the gene encoding the cardiac Na channel, provoke life-threatening cardiac arrhythmias, often by modifying these voltage-dependent conformational changes. These disorders (i.e. the long QT syndrome and Brugada syndrome) may serve as valuable models for understanding the mechanistic linkages between Na channel dysfunction and cardiac arrhythmias in more common, acquired conditions such as cardiac ischemia. In addition, the balance between therapeutic and adverse effects from Na channel blockade by antiarrhythmic compounds may be shifted by subtle alterations in Na channel function. This review examines recent studies that tie key loci in the Na channel primary sequence to its dynamic function, while examining the emerging themes linking Na channel structure, function, and pharmacology to inherited and acquired disorders of cardiac excitability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / metabolism
  • Anti-Arrhythmia Agents / pharmacology*
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / metabolism
  • Binding Sites
  • Electrophysiology
  • Heart / physiology*
  • Humans
  • Ion Channel Gating / physiology*
  • Long QT Syndrome / metabolism
  • Mutation
  • Myocardium / metabolism*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • Sodium Channels / physiology*
  • Structure-Activity Relationship


  • Anti-Arrhythmia Agents
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels