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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 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.
AuthorsChristian Bollensdorff, Andreas Knopp, Christoph Biskup, Thomas Zimmer, Klaus Benndorf
JournalAmerican journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 286 Issue 1 Pg. H283-95 (Jan 2004) ISSN: 0363-6135 [Print] United States
PMID12919930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Potassium Channels
  • Adenosine Triphosphate
  • Sodium
  • Potassium
Topics
  • Adenosine Triphosphate (physiology)
  • Animals
  • Cell Hypoxia
  • Electric Conductivity
  • Electrophysiology
  • Mice
  • Models, Biological
  • Myocardial Ischemia (metabolism)
  • Myocardium (metabolism)
  • Myocytes, Cardiac (metabolism)
  • Oocytes
  • Permeability
  • Potassium (metabolism)
  • Potassium Channels (physiology)
  • Sarcolemma (metabolism)
  • Sodium (metabolism, physiology)
  • Xenopus laevis

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