Cellular K+ loss and anion efflux during myocardial ischemia and metabolic inhibition.
It has been suggested that increased K+ efflux during myocardial hypoxia and ischemia may result from efflux of intracellularly generated anions such as lactate and inorganic phosphate (Pi) as a mechanism of balancing transsarcolemmal charge movement. To investigate this hypothesis cellular K+ loss using 42K+ and K+-sensitive electrodes, intracellular potential, venous lactate and Pi, and tissue lactate and high-energy phosphates were measured in isolated arterially perfused rabbit interventricular septa during exposure to metabolic inhibitors, hypoxia, and ischemia. Selective inhibition of glycolysis caused a marked increase in K+ efflux despite a fall in lactate production and maintenance of normal cellular high-energy phosphate content. During ischemia and hypoxia net loss of lactate and Pi exceeded K+ loss by a factor of 2-6. However, removal of glucose prior to ischemia or during hypoxia increased K+ loss but reduced lactate loss without affecting Pi loss. During hypoxia, 30 mM exogenous lactate did not alter K+ loss in a manner consistent with changes in passive electrodiffusion of lactate ion. These findings inhibition which is not related to anion efflux assumes greater importance under conditions in which glycolysis is inhibited, e.g., ischemia. Under conditions in which glycolysis is not inhibited, e.g., hypoxia, K+ efflux does not parallel passive electrodiffusion of lactate ions. However, this finding does not exclude the possibility that K+ loss could be coupled to carrier-mediated lactate ion efflux.
Weiss
J N
JN
Department of Medicine, University of California School of Medicine, Los Angeles 90024.
Lamp
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Shine
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D006019:Glycolysis; D007473:Ion Channels / Q000502:physiology*; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits
D007473:Ion Channels; D007773:Lactates; D010710:Phosphates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D011188:Potassium; D010100:Oxygen