Effects of pharmacological preconditioning with U50488H on calcium homeostasis in rat ventricular myocytes subjected to metabolic inhibition and anoxia

J. C.S. Ho, S. Wu, K. W.L. Kam, J. S.K. Sham, T. M. Wong

Research output: Contribution to journalArticle

Abstract

1. The effects of pharmacological preconditioning with U50488H (U 50), a selective κ-opioid receptor agonist, on Ca 2+ homeostasis in rat ventricular myocytes subjected for 9 min to metabolic inhibition (MI) and anoxia (A), consequences of ischaemia, were studied and compared with those of preconditioning with brief periods of MI/A. 2. Precondition with 30 μM of U 50 for three cycles of 1 min each cycle separated by 3 min of recovery (UP) significantly increased the percentage of non-blue cells following MI/A. The effect of UP is the same as that of preconditioning with an inhibitor of glycolysis and an oxygen scavenger for three 1-min cycles separated by three-minute recovery (MI/AP). The results indicate that like MI/AP, UP also confers cardioprotection. 3. MI/A increased intracellular Ca 2+ ([Ca 2+] i) and reduced the amplitude of caffeine-induced [Ca 2+] i transients, an indication of Ca 2+ content in the sarcoplasmic reticulum (SR). MI/A also reduced the electrically-induced [Ca 2+] i transient, that indicates Ca 2+-release during excitation-contraction coupling, and Ca 2+ sparks in unstimulated myocytes, that indicates spontaneous Ca 2+-release from SR. It also prolonged the decline of the electrically-induced [Ca 2+] i transient and slowed down the recovery of the electrically-induced [Ca 2+] i transient after administration of caffeine. In addition, MI/A prolonged the decline of caffeine induced [Ca 2+] i transient, an indication of Na +-Ca 2+ exchange activity, and UP prevented it. So UP, that confers cardioprotection, prevented the changes induced by MI/A. With the exception of Ca 2+-spark, which was not studied, the effects of MI/AP are the same as those of UP. 4. It is concluded that pharmacological preconditioning with U 50, that confers immediate cardioprotection, prevents changes of Ca 2+ homeostasis altered by MI/A in the rat heart. This may be responsible, at least partly, for the cardioprotective action. 5. The study also provided evidence that MI/A causes mobilization of Ca 2+ from SR to cytoplasm causing Ca 2+-overload which may be due to reduced Ca 2+-uptake by SR. MI/A also reduces spontaneous and electrically induced Ca 2+ release from SR.

Original languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalBritish Journal of Pharmacology
Volume137
Issue number6
DOIs
StatePublished - Nov 1 2002

Keywords

  • Anoxia
  • Ca homeostasis
  • Ca spark
  • Metabolic inhibition
  • Preconditioning
  • Sarcoplasmic reticulum
  • U50488H
  • Ventricular myocyte
  • κ-opioid receptor

ASJC Scopus subject areas

  • Pharmacology

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