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.
Goto
K
K
Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Kasuya
Y
Y
Matsuki
N
N
Takuwa
Y
Y
Kurihara
H
H
Ishikawa
T
T
Kimura
S
S
Yanagisawa
M
M
Masaki
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects*; D003331:Coronary Vessels; D016232:Endothelins; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D015220:Calcium Channels; D016232:Endothelins; D010455:Peptides; D009529:Nicardipine; D011188:Potassium; D002118:Calcium