Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm

Takeshi Kuga, Hiroaki Shimokawa, Yoji Hirakawa, Yoshiaki Kadokami, Yukinori Arai, Yoshihiro Fukumoto, Kouichi Kuwata, Toshiyuki Kozai, Kensuke Egashira, Akira Takeshita

Research output: Contribution to journalArticle

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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 result-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.

Original languageEnglish
Pages (from-to)822-828
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume35
Issue number5
DOIs
Publication statusPublished - May 22 2000

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L-Type Calcium Channels
Muscle Spasticity
Spasm
Vascular Smooth Muscle
Smooth Muscle Myocytes
Coronary Vessels
Swine
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Nifedipine
Serotonin
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm. / Kuga, Takeshi; Shimokawa, Hiroaki; Hirakawa, Yoji; Kadokami, Yoshiaki; Arai, Yukinori; Fukumoto, Yoshihiro; Kuwata, Kouichi; Kozai, Toshiyuki; Egashira, Kensuke; Takeshita, Akira.

In: Journal of Cardiovascular Pharmacology, Vol. 35, No. 5, 22.05.2000, p. 822-828.

Research output: Contribution to journalArticle

Kuga, Takeshi ; Shimokawa, Hiroaki ; Hirakawa, Yoji ; Kadokami, Yoshiaki ; Arai, Yukinori ; Fukumoto, Yoshihiro ; Kuwata, Kouichi ; Kozai, Toshiyuki ; Egashira, Kensuke ; Takeshita, Akira. / Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm. In: Journal of Cardiovascular Pharmacology. 2000 ; Vol. 35, No. 5. pp. 822-828.
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AU - Kadokami, Yoshiaki

AU - Arai, Yukinori

AU - Fukumoto, Yoshihiro

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