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

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 i(NaCa) 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 i(NaCa) 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 i(NaCa) or complete block of both inward and outward i(NaCa) on the action potentials 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 glucoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an ontward shift in i(NaCa) at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward i(NaCa) and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action when a muscle is allowed to shorten during the action potential. Inward i(NaCa) may play an important role in both normal pacemaker activity in the heart.