An endogenous Ca2+ channel agonist, endothelin-1, does not directly activate partially purified dihydropyridine-sensitive Ca2+ channel from cardiac muscle in a reconstituted system.

To elucidate the action of tentative endogenous Ca2+ channel activator, endothelin (ET)-1, on a voltage-dependent Ca2+ channel in the heart, a dihydropyridine (DHP)-binding protein was solubilized from porcine ventricular muscle, partially purified by wheat germ agglutinin-affinity chromatography and reconstituted into proteoliposomes. Ca2+ flux into the proteoliposomes was determined using a fluorescent probe, Quin-2. The initial Ca2+ entry rate was dose-dependently activated by either a K(+)-depolarization or a synthetic Ca2+ channel agonist, Bay K8644, and inhibited by several Ca2+ entry blockers or cadmium ions. Using the same reconstituted system, it was demonstrated that sufficient dose of ET-1 yielded no effect on the Ca2+ channel function, indicating that the ET-1 action was not directly mediated by the voltage-dependent, DHP-sensitive Ca2+ channel.