Sarcolemmal Na+-Ca2+ exchange activity in hearts subjected to hypoxia reoxygenation.
Although the occurrence of intracellular Ca2+ overload is known to be an important factor in hypoxia-reoxygenation injury, the exact mechanisms for this abnormality are not presently clear. Since Na+-Ca2+ exchange in the sarcolemmal membrane is considered to be involved in Ca2+ efflux, this study was undertaken to examine the effect of hypoxia reoxygenation on this system. Isolated rat hearts were made hypoxic by perfusing with a substrate-free medium gassed with 95% N2-5% CO2 and then reperfused with oxygenated normal medium. Hypoxia was found to markedly increase the resting tension and depress the ability of the heart to generate contractile force; reoxygenation resulted in partial recovery of these parameters. Sarcolemmal vesicles were isolated from control, hypoxic, and hypoxia-reoxygenated hearts, and the Na+-dependent Ca2+ uptake activity was measured at different times of incubation as well as at different concentrations of calcium. Sarcolemmal ATP-dependent Ca2+ accumulation was also measured for the purpose of comparison. A significant decrease in Na+-dependent Ca2+ uptake was observed in preparations from hearts made hypoxic for 10 min. Reoxygenation of 10-min hypoxic hearts resulted in a further depression of Na+-Ca2+ exchange activity. ATP-dependent Ca2+ accumulation was also depressed in hypoxic as well as reoxygenated hearts. These results suggest a defect in the Na+-Ca2+ exchange system and the ATP-dependent Ca2+ pump in the heart sarcolemmal membrane, and this may contribute to the occurrence of intracellular Ca2+ overload and functional abnormalities due to hypoxia-reoxygenation injury.
Dixon
I M
IM
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Center, Winnipeg, Canada.
Eyolfson
D A
DA
Dhalla
N S
NS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000032:analysis; D008565:Membrane Proteins / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000201:enzymology / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D008563:Membrane Lipids; D008565:Membrane Proteins; D019831:Sodium-Calcium Exchanger; D000255:Adenosine Triphosphate; D012964:Sodium; D010100:Oxygen; D002118:Calcium