Competitive interactions of sodium and calcium with the sodium-calcium exchange system of cardiac sarcolemmal vesicles.
The initial velocity of Ca2+ uptake via the Na-Ca exchange system in cardiac sarcolemmal vesicles is competitively inhibited by extravesicular Na+. The Hill plots for multisite competitive inhibition are nonlinear, exhibiting a limiting slope of 1 at low Na+ concentrations (less than 20 mM) and 1.6-2.0 at higher concentrations. The Ki for Na+ is approximately 16 mM. Thus, the Ca2+ binding site of the Na-Ca exchange carrier interacts with either 1 or 2 Na+ ions and the binding of a single Na+ is sufficient to block Ca2+ binding. These results, in conjunction with the observation that at least 3 Na+ ions are required at the trans membrane surface to bring about Ca2+ movements by Na-Ca exchange, suggest that the exchange carrier contains two classes of cation binding sites: a divalent site which can bind either 1 Ca2+ or 1-2 Na+ ions and a second site which binds at least one additional Na+. The classical observation that cardiac contractility depends upon the [Ca2+]/[Na+]2 ratio of the extracellular medium can be readily explained in terms of the competitive interactions of Na+ and Ca2+ at the divalent site.
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium