title: Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion.
abstract: OBJECTIVE
  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 [Ca2+]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.
  
  
  CONCLUSIONS
  The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/reperfusion.
authors.affiliation: The Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Cao
authors.forename: Wing-yee
authors.initials: WY
authors.lastname: Yan
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Kenneth W L
authors.initials: KW
authors.lastname: Kam
authors.forename: Shi-zhong
authors.initials: SZ
authors.lastname: Zhan
authors.forename: James S K
authors.initials: JS
authors.lastname: Sham
authors.forename: Tak-ming
authors.initials: TM
authors.lastname: Wong
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D012430:Ruthenium Red; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium