Modulation of ATP-dependent calcium extrusion and Na+/Ca2+ exchange across rat cardiac sarcolemma by calcium antagonists.

The calcium antagonists verapamil, bepridil, nifedipine and nimodipine inhibited ATP-dependent 45Ca2+ uptake in purified rat ventricular sarcolemma vesicles dose dependently. This inhibition was preceded by a slight stimulation in the case of the two dihydropyridines, but not with bepridil and verapamil. In contrast, Na+/Ca2+ exchange was only inhibited by verapamil and bepridil and not affected by the dihydropyridines. The steepness of the inhibition curves was significantly different for the two processes. No stereoselectivity was found with either process for inhibition by the verapamil enantiomers. Inhibition of the exchange was not due to a decrease of the exchange velocity but to a decrease in exchange capacity. Variation of the antagonist preincubation time did not modify the inhibition of the uptake. The results indicate that two different sites, located at the inner surface of the sarcolemma are involved in the modulation of the ATP-dependent uptake and the Na+/Ca2+ exchange. However, the possibility cannot be ruled out that inhibition of the exchange process is also mediated by an extracellularly located site.