Effects of dihydropyridines on calcium release from the isolated membrane complex consisting of the transvere tubule and sarcoplasmic reticulum

We have investigated a) the effects of the dihydropyridines (DHPs) nifedipine and nimodipine on depolarization-induced (T-tubule-mediated) Ca²⁺ release in the vesicles consisting of the complex of the T-tubule and SR, and b) the binding of [³H]nimodipine to these vesicles. These DHPs inhibited the slow but not the fast phase of depolarization-induced release, both of which are mediated via the T-tubule. The DHPs have no effect on caffeine-induced release in which T-tubules are not involved. There are two classes of DHP binding sites: one, with high affinity and small capacity, and another, exhibiting low affinity and a much larger capacity. The inhibition paralleled the low affinity binding of DHP with no correlation with the high affinity binding. These results suggest that the low affinity DHP binding sites located probably in the DHP receptor, rather than the high affinity DHP binding site, are responsible for the inhibition of e-c coupling.