TY - JOUR
T1 - Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion
AU - Cao, Chun Mei
AU - Yan, Wing Yee
AU - Liu, Jing
AU - WL Kam, Kenneth
AU - Zhan, Shi Zhong
AU - Sham, James S.K.
AU - Wong, Tak Ming
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
KW - BAPTA-AM
KW - Cardiac myocytes
KW - Electrically-induced Ca transient
KW - Infarct size
KW - Isolated perfused rat heart
KW - Ruthenium red
UR - http://www.scopus.com/inward/record.url?scp=33748520910&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748520910&partnerID=8YFLogxK
U2 - 10.1111/j.1745-7254.2006.00391.x
DO - 10.1111/j.1745-7254.2006.00391.x
M3 - Article
C2 - 16787576
AN - SCOPUS:33748520910
SN - 1671-4083
VL - 27
SP - 911
EP - 918
JO - Acta Pharmacologica Sinica
JF - Acta Pharmacologica Sinica
IS - 7
ER -