Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion

Chun Mei Cao, Wing Yee Yan, Jing Liu, Kenneth WL Kam, Shi Zhong Zhan, James S.K. Sham, Tak Ming Wong

Research output: Contribution to journalArticle

Abstract

Aim: Attenuation of mitochondrial Ca2+ ([Ca2+] m), but not cytosolic Ca2+ ([Ca2+] c), overload improves contractile recovery. We hypothesized that attenuation of [Ca2+]m, but not [Ca2+] c, overload confers cardioprotection against ischemia/reperfusion- induced injury. Methods: Infarct size from isolated perfused rat heart, cell viability, and electrically-induced Ca2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca 2+]m, but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca2+]m in cardioprotection and contractile recovery in response to ischemia/reperfusion. Conclusion: The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca 2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca 2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/reperfusion.

Original languageEnglish (US)
Pages (from-to)911-918
Number of pages8
JournalActa Pharmacologica Sinica
Volume27
Issue number7
DOIs
StatePublished - Jul 1 2006

    Fingerprint

Keywords

  • BAPTA-AM
  • Cardiac myocytes
  • Electrically-induced Ca transient
  • Infarct size
  • Isolated perfused rat heart
  • Ruthenium red

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this