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 I KATP,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.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||1 55-1|
|Publication status||Published - 1 Jan 2004|
- K efflux
- Na influx
ASJC Scopus subject areas