Na+ current through KATP channels:: consequences for Na+ and K+ fluxes during early myocardial ischemia

During early myocardial ischemia, the myocytes are loaded with Na+, which in turn leads to Ca2+ overload and cell death. The pathway of the Na+ influx has not been fully elucidated. The aim of the study was to quantify the Na+ inward current through sarcolemmal K-ATP channels (I-KATP,I- Na) in anoxic isolated cardiomyocytes at the actual reversal potential (V-rev) and to estimate the contribution of this current to the Na+ influx in the ischemic myocardium. I-KATP, Na was determined in excised single channel patches of mouse ventricular myocytes and macropatches of Xenopus laevis oocytes expressing SUR2A/Kir6.2 channels. In the presence of K+ ions, the respective permeability ratios for Na+ to K+ ions, P-Na/P-K, were close to 0.01. Only in the presence of Na+ ions on both sides of the membrane was I-KATP,I- Na similarly large to that calculated from the permeability ratio P-Na/P-K, indicative of a Na+ influx that is largely independent of the K+ efflux at V-rev. With the use of a peak K-ATP channel conductance in anoxic cardiomyocytes of 410 nS, model simulations for a myocyte within the ischemic myocardium showed that the amplitude of the Na+ influx and K+ efflux is even larger than the respective fluxes by the Na+-K+ pump and all other background fluxes. These results suggest that during early ischemia the Na+ influx through K-ATP channels essentially contributes to the total Na+ influx and that it also balances the K+ efflux through K-ATP channels.