Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum.
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
N
N
Department of Physiology, University of Nevada School of Medicine, Reno 89557-0046.
Hume
J R
JR
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D004553:Electric Conductivity; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D015737:Nisoldipine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin / Q000494:pharmacology
D002352:Carrier Proteins; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D005711:Gallopamil; D013779:Tetrodotoxin; D015737:Nisoldipine; D012964:Sodium; D002118:Calcium