Anoxia Depresses Sodium–Calcium Exchange Currents in Guinea-pig Ventricular Myocytes

Cardiac Na–Ca exchange is related to the intracellular calcium overload that occurs during ischemia and reperfusion. However, direct observation of the membrane current through Na–Ca exchange during ischemia has not been performed. The purpose of this study was to clarify the effect of simulated ischemia (substrate-free anoxia) and intracellular acidification on the Na–Ca exchange current. The electrogenic Na–Ca exchange current was recorded from isolated guinea-pig ventricular myocytes by using patch-clamp techniques. Exposure to anoxia significantly decreased both the inward and outward directed Na–Ca exchange currents (from −1.21±0.18 to −0.04±0.32 pA/pF at −80 mV; from 6.58±1.06 to 3.14±1.06 pA/pF at +40 mV). The reversal potential of Na–Ca exchange current shifted to negative direction during anoxia. Subsequent reoxygenation rapidly restored the amplitude of exchange currents and the reversal potential. These anoxia/reoxygenation-induced changes were completely inhibited when the intracellular pH was clamped at 7.3 by using 20 m HEPES-buffer. Furthermore, the anoxia-induced changes of Na–Ca exchange current were mimicked by the intracellular acidosis induced by a brief exposure to ammonium chloride in normoxic conditions. We conclude that the Cardiac Na–Ca exchange is suppressed by anoxia secondary to intracellular acidosis, and that these changes were reversed by reoxygenation.