AJP - Heart and Circulatory Physiology, Vol 259, Issue 3 962-H972, Copyright © 1990 by American Physiological Society

ARTICLES

Activation of furosemide-sensitive K+ fluxes in myocytes by ouabain and recovery from metabolic inhibition

O. Kohmoto, J. A. Krueger and W. H. Barry
Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132.

Modulation of transsarcolemmal K+ flux mediated by the furosemide-sensitive K(+)-Cl- (or Na(+)-K(+)-Cl-) cotransport carrier was studied in cultured chick embryo ventricular cells. We defined at least three distinct K+ efflux pathways: 1) a Ba2(+)-sensitive efflux component, probably reflecting K+ movement through K+ channels; 2) a furosemide-sensitive component, reflecting K(+)-Cl- cotransport; and 3) a component insensitive to both Ba2+ and furosemide. With respect to K+ influx, there were 1) a ouabain-sensitive K+ uptake presumably mediated by Na(+)-K(+)-adenosinetriphosphatase and 2) a furosemide-sensitive K+ uptake. The effects of elevation of intracellular calcium concentration ([Ca2+]i) on Ba2+ and furosemide-sensitive K+ flux pathways were studied. Elevation of [Ca2+]i had minor effects on Ba2(+)-sensitive K+ flux. However, elevation of [Ca2+]i produced by exposure to ouabain for 60 min activated a furosemide-sensitive 42K+ efflux and a ouabain-resistant, furosemide-sensitive 42K+ influx. The activation of K+ influx, caused by an increase in [Ca2+]i, was completely inhibited by ATP depletion (produced by exposure to ouabain and metabolic inhibitors simultaneously) and was partially inhibited by the calmodulin inhibitor W7. Activation of the furosemide-sensitive K+ flux was also produced by washout of metabolic inhibitors, a condition in which ATP resynthesis occurs in the presence of an increased [Ca2+]i. Activation of furosemide-sensitive K+ fluxes by exposure to ouabain or washout of metabolic inhibitors caused a net K+ loss, which accounts in part for the cell shrinkage noted during recovery from metabolic inhibition in previous studies. These results suggest that [Ca2+]i and intracellular ATP concentration are important in the regulation of furosemide-sensitive K+ flux in these cells, perhaps via the involvement of a Ca2(+)-calmodulin-dependent protein kinase.

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