The role of Na-Ca exchange current in the cardiac action potential

Cardiovasc Res. 1996 Jul;32(1):69-84.


Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Publication types

  • Review

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Arrhythmias, Cardiac / physiopathology
  • Biological Transport, Active
  • Calcium / metabolism*
  • Carrier Proteins / metabolism*
  • Humans
  • Ion Transport
  • Myocardium / metabolism*
  • Sinoatrial Node / physiology
  • Sodium / metabolism*
  • Sodium-Calcium Exchanger


  • Carrier Proteins
  • Sodium-Calcium Exchanger
  • Sodium
  • Calcium