Verapamil, diltiazem and nifedipine interactions with calmodulin stimulated (Ca super(2+) + Mg super(2+))-ATPase

The functional interactions of the three prototype Ca super(2+) antagonists, verapamil, diltiazem and nifedipine, were examined in relation to the calmodulin regulated plasma membrane Ca super(2+) pump ATPase. Unlike dihydropyridine modulation of verapamil and diltiazem binding at high affinity channel sites, nifedipine in this system did not alter the inhibitory responses of verapamil and diltiazem. The calmodulin directed antagonism of the two drugs was shown to be strictly additive over a full range of calmodulin concentrations. This model system provides evidence for additional functional discrepancies among the various classes of Ca super(2+) antagonists.