Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca²⁺ channel in vascular smooth muscle

Endothelin is a potent endothelium-derived vasoconstrictor peptide recently characterized from porcine and human vascular endothelial cells. Here we provide evidence that endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca²⁺ channel in porcine coronary artery smooth muscle. The vasoconstrictor action of endothelin is efficiently antagonized by low doses of the dihydropyridine Ca²⁺-channel blocker nicardipine. Endothelin augments the Ca²⁺-induced contraction in a high-K⁺ depolarizing solution, markedly enhances high-threshold Ca²⁺-channel current on the whole-cell patch clamp recording, and causes a sustained increase in the intracellular Ca²⁺ that is largely dependent on extracellular Ca²⁺. These findings suggest that endothelin exerts its vasoconstrictor effect by either directly or indirectly activating the voltage-dependent Ca²⁺ channel.