SUBUNIT-DEPENDENT MODULATION OF RECOMBINANT L-TYPE CALCIUM CHANNELS -MOLECULAR-BASIS FOR DIHYDROPYRIDINE TISSUE SELECTIVITY

At least four calcium channel subtypes (P, T, N, and L) have now been classified on the basis of their biophysical and/or pharmacological pr operties. L-type channels, a channel family particularly important to physiological function of the cardiovascular system, are identified by their slow voltage- and calcium-dependent inactivation as well as the ir sensitivity to dihydropyridine (DHP) calcium channel antagonists. I n this study, we report the results of experiments in which we have me asured the DHP modulation of recombinant calcium channel activity in c ells transfected with alpha1 subunits of cardiac and smooth muscle L-t ype calcium channels. We find subunit-dependent differences in the vol tage and concentration dependence of channel modulation. Our results p rovide evidence for a molecular basis for DHP sensitivity of heart and smooth muscle calcium channels and, additionally, indicate that, even within one family of calcium channels, slight differences in channel structure can cause marked differences in channel pharmacology.