Open AccessAttenuation of mitochondrial, but not cytosolic, Ca 2+ overload reduces myocardial injury induced by ischemia and reperfusion 1
Author(s) -
CAO Chunmei,
YAN Wingyee,
LIU Jing,
WL KAM Kenneth,
ZHAN Shizhong,
SHAM James SK,
WONG Takming
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00391.x
Subject(s) - cardioprotection , ischemia , ruthenium red , cytosol , reperfusion injury , bapta , chemistry , medicine , calcium , myocyte , uniporter , cardiology , pharmacology , biochemistry , enzyme
Aim: Attenuation of mitochondrial Ca 2+ ([Ca 2+ ] m ), but not cytosolic Ca 2+ ([Ca 2+ ] c ), overload improves contractile recovery. We hypothesized that attenuation of [Ca 2+ ] m , but not [Ca 2+ ] c , overload confers cardioprotection against ischemia/ reperfusion‐induced injury. Methods : Infarct size from isolated perfused rat heart, cell viability, and electrically‐induced Ca 2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA‐AM, a Ca 2+ chelator, at concentrations that abolish the overload of both [Ca 2+ ] c and [Ca 2+ ] m , and ruthenium red, an inhibitor of mitochondrial uniporter of Ca 2+ transport, at concentrations that abolish the overload of [Ca 2+ ] m , but not [Ca 2+ ] c , on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca 2+ ] m and [Ca 2+ ] c by BAPTA‐AM, and attenuation of [Ca 2+ ] m , but not [Ca 2+ ] c , overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] c , by ruthenium red improves contractile recovery following ischemia/ reperfusion.