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+]ibut 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+]ior on intracellular pH during ischemia. However, there was a short-lived increase in [Na+]iof 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+]iduring anoxia. The [Na+]idid not change during 10 min of anoxia, but there was a small, transient rise of [Na+]ion 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.