AHEART May 45/5

Park, Choon-Ok, Xiao-Hui Xiao, and David G. Allen. Changes in intracellular Na1 and pH in rat heart during ischemia: role of Na1/H1 exchanger. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H1581–H1590, 1999.—The role of the Na1/H1 exchanger in rat hearts during ischemia and reperfusion was investigated by measurements of intracellular Na1 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 Na1/H1 exchanger was inactive during ischemia. This was confirmed by showing that the Na1/H1 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 6 0.6 mM on reperfusion, which was reduced by MIA, showing that the Na1/H1 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 Na1/H1 exchanger, tested by sodium lactate exposure, was inhibited during anoxia. These results show that the Na1/H1 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.