Alterations in cardiac membrane Ca2+ transport during oxidative stress

• DOI: 10.1007/bf00230342
• Publication Date: 2004-09-07T02:07:33Z
• Authors: IanM.C. Dixon; Masanori Kaneko; Tomoji Hata; Vincenzo Panagia; NaranjanS. Dhalla
• Keywords: Male; 0301 basic medicine; Free Radicals; Hydroxyl Radical; Myocardium; Sodium; Biological Transport; Myocardial Reperfusion Injury; Rats, Inbred Strains; Calcium-Transporting ATPases; Hydrogen Peroxide; Rats; Oxygen; Kinetics; 03 medical and health sciences; Sarcolemma; Superoxides; Hydroxides; Animals; Calcium; Oxidation-Reduction

Although cardiac dysfunction due to ischemia-reperfusion injury is considered to involve oxygen free radicals, the exact manner by which this oxidative stress affects the myocardium is not clear. As the occurrence of intracellular Ca2+ overload has been shown to play a critical role in the genesis of cellular damage due to ischemia-reperfusion, this study was undertaken to examine whether oxygen free radicals are involved in altering the sarcolemmal Ca2(+)-transport activities due to reperfusion injury. When isolated rat hearts were made globally ischemic for 30 min and then reperfused for 5 min, the Ca2(+)-pump and Na(+)-Ca2+ exchange activities were depressed in the purified sarcolemmal fraction; these alterations were prevented when a free radical scavenger enzymes (superoxide dismutase plus catalase) were added to the reperfusion medium. Both the Ca2(+)-pump and Na(+)-Ca2+ exchange activities in control heart sarcolemmal preparations were depressed by activated oxygen-generating systems containing xanthine plus xanthine oxidase and H2O2; these changes were prevented by the inclusion of superoxide dismutase and catalase in the incubation medium. These results support the view that oxidative stress during ischemia-reperfusion may contribute towards the occurrence of intracellular Ca2+ overload and subsequent cell damage by depressing the sarcolemmal mechanisms governing the efflux of Ca2+ from the cardiac cell.