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

1989; National Academy of Sciences; Volume: 86; Issue: 10 Linguagem: Inglês

10.1073/pnas.86.10.3915

1091-6490

Katsutoshi Goto, Yoshitoshi Kasuya, Norio Matsuki, Yoh Takuwa, Hiroki Kurihara, Tomohisa Ishikawa, Sadao Kimura, Masashi Yanagisawa, Takao Masaki,

Signaling Pathways in Disease

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.