Changes in intracellular Na+ and pH in rat heart during ischemia: role of Na+/H+ exchanger.
The role of the Na+/H+ exchanger in rat hearts during ischemia and reperfusion was investigated by measurements of intracellular Na+ concentration ([Na+]i) and intracellular and extracellular pH. Under our standard conditions (2-Hz stimulation), 10 min of ischemia caused no significant rise in [Na+]i but an acidosis of 1.0 pH unit, suggesting that the Na+/H+ exchanger was inactive during ischemia. This was confirmed by showing that the Na+/H+ exchange inhibitor methylisobutyl amiloride (MIA) had no effect on [Na+]i or on intracellular pH during ischemia. However, there was a short-lived increase in [Na+]i of 8.2 +/- 0.6 mM on reperfusion, which was reduced by MIA, showing that the Na+/H+ exchanger became active on reperfusion. To investigate the role of metabolic changes, we measured [Na+]i during anoxia. The [Na+]i did not change during 10 min of anoxia, but there was a small, transient rise of [Na+]i on reoxygenation, which was inhibited by MIA. In addition, we show that the Na+/H+ exchanger, tested by sodium lactate exposure, was inhibited during anoxia. These results show that the Na+/H+ exchanger is inhibited during ischemia and anoxia, probably by an intracellular metabolic mechanism. The exchanger activates rapidly on reperfusion and can cause a rapid rise in [Na+]i.
D000138:Acidosis / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001578:Benzopyrans; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D019354:Sodium Lactate / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects