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.
The Second Department of Internal Medicine, University of Tokyo, Japan.
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Naitoh
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Toyo-Oka
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Sugimoto
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D017275:Isradipine; D007700:Kinetics; D008081:Liposomes; D008861:Microsomes / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D011510:Proteolipids; D012508:Sarcolemma / Q000502:physiology; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D016232:Endothelins; D008081:Liposomes; D010069:Oxadiazoles; D011510:Proteolipids; C020485:proteoliposomes; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium; D017275:Isradipine