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

Abstract

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 KATP channels ( IKATP,Na) in anoxic isolated cardiomyocytes at the actual reversal potential ( Vrev) and to estimate the contribution of this current to the Na+ influx in the ischemic myocardium. IKATP,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, PNa/ PK, were close to 0.01. Only in the presence of Na+ ions on both sides of the membrane was IKATP,Na similarly large to that calculated from the permeability ratio PNa/ PK, indicative of a Na+ influx that is largely independent of the K+ efflux at Vrev. With the use of a peak KATP 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 KATP channels essentially contributes to the total Na+ influx and that it also balances the K+ efflux through KATP channels.