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 journalArticlepeer-review

9 Citations (Scopus)

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 - 2000

Keywords

  • Bay K 8644
  • Coronary spasm
  • L-type calcium channel
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm'. Together they form a unique fingerprint.

Cite this