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 Ca(2+) 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.
Bollensdorff
Christian
C
Institut für Physiologie, Friedrich-Schiller-Universität Jena, Teichgraben 8, D-07740 Jena, Germany.
Knopp
Andreas
A
Biskup
Christoph
C
Zimmer
Thomas
T
Benndorf
Klaus
K
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015687:Cell Hypoxia; D004553:Electric Conductivity; D004594:Electrophysiology; D051379:Mice; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009865:Oocytes; D010539:Permeability; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D012964:Sodium; D011188:Potassium