Sodium channel (dys)function and cardiac arrhythmias

Cardiovasc Ther. 2010 Oct;28(5):287-94. doi: 10.1111/j.1755-5922.2010.00210.x. Epub 2010 Jul 14.


Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation and propagation of action potentials throughout the myocardium and consequently plays a central role in excitability of myocardial cells and proper conduction of the electrical impulse within the heart. The importance of sodium channels for normal cardiac electrical activity is emphasized by the occurrence of potentially lethal arrhythmias in the setting of inherited and acquired sodium channel disease. During common pathological conditions such as myocardial ischemia and heart failure, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. In addition, sodium channel dysfunction caused by mutations in the SCN5A gene, encoding the major sodium channel in heart, is associated with a number of arrhythmia syndromes. Here, we provide an overview of the structure and function of the cardiac sodium channel, the clinical and biophysical characteristics of inherited and acquired sodium channel dysfunction, and the (limited) therapeutic options for the treatment of cardiac sodium channel disease.

Publication types

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

MeSH terms

  • Action Potentials
  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / physiopathology
  • Genetic Predisposition to Disease
  • Humans
  • Muscle Proteins / metabolism
  • Mutation
  • Myocytes, Cardiac / metabolism*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Protein Conformation
  • Sodium Channels / chemistry
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Structure-Activity Relationship


  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels