Oxidant injury to isolated heart cells.
Recent evidence suggests that free radicals are generated in the heart during the reperfusion which follows ischemia. Intracellular accumulation of calcium has been postulated to be an important pathogenic factor in a number of disease states, including reperfusion injury. Therefore, in this study, the effects of various oxidants on calcium uptake by isolated rat heart cells were investigated. Ammonium persulphate, t-butyl hydroperoxide and phenazine methosulphate increased the number of cells in contracture in both a concentration dependent and time dependent manner, while 45Ca content of cardiomyocytes was decreased by oxidant in proportion to its concentration. Carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) dependent (mitochondrial) and CCCP independent (sarcoplasmic reticulum) 45Ca contents in chemically skinned myocytes were reduced by the oxidants. By contrast, hydrogen peroxide raised 45Ca content of cardiomyocytes and did not reduce sarcoplasmic reticulum 45Ca content, although mitochondrial 45Ca content was decreased. Release of 45Ca from mitochondria and sarcoplasmic reticulum in saponin treated myocytes was accelerated by hypochlorous acid and hydrogen peroxide. The authors conclude that oxidants other than hydrogen peroxide inhibited intracellular uptake of calcium and accelerated calcium release, thus raising the cytosolic calcium concentration and causing cell contracture. The net influx of calcium across sarcolemmal membrane was decreased by these oxidants.
Kaminishi
K
K
Department of Physiology, University of Ottawa, School of Medicine, Ontario.
Yanagishita
T
T
Kako
K J
KJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology*; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D005609:Free Radicals; D006861:Hydrogen Peroxide; D002118:Calcium