Specific binding of a calcium channel activator, [³H]BAY k 8644, to membranes from cardiac muscle and brain

BAY k 8644 is a member of a new class of drugs that directly activates Ca²⁺ channels. This 1,4-dihydropyridine was found to bind to both high and low affinity sites on rabbit ventricular microsomes and guinea pig brain synaptosomes. The dissociation constant obtained from Scatchard analysis with [³H]BAY k 8644 was 2 to 3 nM for the high affinity binding site, and the estimated maximal number of binding sites was 0.8 and 0.4 pmol/mg protein for heart and brain membranes, respectively, at 15°C. Competition between nitrendipine and [³H]BAY k 8644 indicated a common high affinity binding site for Ca²⁺ channel activators and antagonists. The results suggest that the 1,4-dihydropyridine Ca²⁺ channel antagonists do not act as simple channel plugs.