K+ channel openers, cromakalim and Ki4032, inhibit agonist-induced Ca2+ release in canine coronary artery

Toshio Yamagishi, Teruyuki Yanagisawa, Norio Taira

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

The effects of K+ channel openers, cromakalim and an acetoxyl derivative of KRN 2391 (Ki 4032), were studied on force of contraction, increases in intracellular calcium concentration ([Ca2+]i) measured by fura-2 and inositol 1,4,5-trisphosphate (IP3) production induced by the thromboxane A2 analogue, U46619, in canine coronary arteries. Upon single dose applications of U46619 at 300 nmol/l, phasic and tonic increases in [Ca2+]i and force were seen, which were almost abolished by cromakalim (10 μmol/l) and Ki4032 (100 μmol/l).In the absence of extracellular Ca2+, U46619 induced a transient increase in [Ca2+]i with a contraction. Cromakalim (0.01–10 μmol/l) and Ki4032 (0.1–100 μmol/l) concentration-dependently inhibited the increases in [Ca2+]i and contraction. The inhibitory effects of cromakalim and Ki4032 were blocked by the K+ channel blocker tetrabutylammonium (TBA) and counteracted by 20 mmol/l KCl-induced depolarization. Cromakalim and Ki4032 did not affect caffeine-induced Ca2+ release. Cromakalim reduced U46619-induced IP3 production significantly and TBA blocked this inhibitory effect. These results suggest that the hyperpolarization of the plasma membrane by K+ channel openers inhibits the production of IP3 and Ca 2+ release from intracellular stores related to stimulation of the thromboxane A2 receptor.

Original languageEnglish
Pages (from-to)691-700
Number of pages10
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume346
Issue number6
DOIs
Publication statusPublished - 1992 Dec

Keywords

  • Ca release
  • Inositol 1,4,5-trisphosphate
  • K channel openers
  • Tetrabutylammonium (TBA)
  • Thromboxane A analogue

ASJC Scopus subject areas

  • Pharmacology

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