Anoxia depresses sodium-calcium exchange currents in guinea-pig ventricular myocytes.

Abstract

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 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.