%0 Journal Article %T Attenuation of mitochondrial, but not cytosolic, Ca 2+ overload reduces myocardial injury induced by ischemia and reperfusion %A Cao Chun-mei %A Yan Wing-yee %A Liu Jing %A Kam Kenneth Wl %A Zhan Shi-zhong %A Sham James SK %A Wong Tak-ming %J Acta Pharmacologica Sinica %D 2016 %B 2016 %9 %! Attenuation of mitochondrial, but not cytosolic, Ca 2+ overload reduces myocardial injury induced by ischemia and reperfusion %K %X 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. %U http://www.chinaphar.com/article/view/4018 %V 27 %N 7 %P 911–918 %@ 1745-7254