title: Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm.
abstract: Coronary artery spasm is caused primarily by increased contractility of vascular smooth muscle. Excessive Ca2+ entry into vascular smooth muscle cells (VSMCs) may be one of the key mechanisms for the spasm, but no study has ever directly examined the possible alterations of Ca2+ channels in the spastic coronary artery. Here we show that L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery. In a porcine model of coronary spasm with balloon injury, both receptor-mediated stimulation of L-type Ca2+ channels by serotonin and direct stimulation of the channels by Bay K 8644 (a dihydropyridine Ca2+ channel agonist) repeatedly induced coronary spasm in vivo, which was abolished by pretreatment with nifedipine, a dihydropyridine Ca2+ channel antagonist. In a single VSMC freshly dispersed from coronary arteries in vitro, patch-clamp experiments showed that current density of L-type Ca2+ channel current was significantly increased in VSMCs from the spastic site compared with that from the control site even when the channels were maximally stimulated by Bay K 8644. There was no difference in the sensitivity of the channels to Bay K 8644. These results indicate that functionally available L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery in our porcine model, suggesting that increased expression of L-type Ca2+ channels and concomitant increase in Ca2+ entry into VSMCs through the channels may contribute, at least in part, to the pathogenesis of coronary artery spasm.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuga
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hirakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kadokami
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: K
authors.initials: K
authors.lastname: Kuwata
authors.forename: T
authors.initials: T
authors.lastname: Kozai
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000378:metabolism; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D013552:Swine
chemical_list: D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester