Sodium entry through tetrodotoxin-sensitive channels triggered calcium release from the sarcoplasmic reticulum via sodium-calcium exchange in isolated cardiac myocytes.
Sodium entry through sodium channels can trigger sarcoplasmic calcium release via sodium-calcium exchange, providing a mechanistic explanation for the inotropic effects of cardiac glycosides and certain antiarrhythmic drugs.
The role of sodium-calcium exchange at the sarcolemma in the release of calcium from cardiac sarcoplasmic reticulum was investigated in voltage-clamped, isolated cardiac myocytes. In the absence of calcium entry through voltage-dependent calcium channels, membrane depolarization elicited release of calcium from ryanodine-sensitive internal stores. This process was dependent on sodium entry through tetrodotoxin-sensitive sodium channels. Calcium release under these conditions was also dependent on extracellular calcium concentration, suggesting a calcium-induced trigger release mechanism that involves calcium entry into the cell by sodium-calcium exchange. This sodium current-induced calcium release mechanism may explain, in part, the positive inotropic effects of cardiac glycosides and the negative inotropic effects of a variety of antiarrhythmic drugs that interact with cardiac sodium channels. In response to a transient rise of intracellular sodium, sodium-calcium exchange may promote calcium entry into cardiac cells and trigger sarcoplasmic calcium release during physiologic action potentials.
Leblanc et al. (1990) studied Isolated cardiac myocytes. Membrane depolarization was evaluated on Release of calcium from cardiac sarcoplasmic reticulum. Sodium entry through tetrodotoxin-sensitive channels triggered calcium release from the sarcoplasmic reticulum via sodium-calcium exchange in isolated cardiac myocytes.