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Am J Physiol Renal Physiol 282: F91-F102, 2002. First published August 21, 2001; doi:10.1152/ajprenal.0141.2001
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Vol. 282, Issue 1, F91-F102, January 2002

In rat inner medullary collecting duct, NH<UP><SUB>4</SUB><SUP>+</SUP></UP> uptake by the Na,K-ATPase is increased during hypokalemia

Susan M. Wall1, Michael P. Fischer1, Gheun-Ho Kim2, Bich-May Nguyen1, and Kathryn A. Hassell1

1 University of Texas, Medical School at Houston, Houston, Texas 77030; and 2 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892

In rat terminal inner medullary collecting duct (tIMCD), the Na,K-ATPase mediates NH<UP><SUB>4</SUB><SUP>+</SUP></UP> uptake, which increases secretion of net H+ equivalents. K+ and NH<UP><SUB>4</SUB><SUP>+</SUP></UP> compete for a common binding site on the Na,K-ATPase. Therefore, NH<UP><SUB>4</SUB><SUP>+</SUP></UP> uptake should increase during hypokalemia because interstitial K+ concentration is reduced. We asked whether upregulation of the Na,K-ATPase during hypokalemia also increases basolateral NH<UP><SUB>4</SUB><SUP>+</SUP></UP> uptake. To induce hypokalemia, rats ate a diet with a low K+ content. In tIMCD tubules from rats given 3 days of dietary K+ restriction, Na,K-ATPase beta 1-subunit (NK-beta 1) protein expression increased although NK-alpha 1 protein expression and Na,K-ATPase activity were unchanged relative to K+-replete controls. However, after 7 days of K+ restriction, both NK-alpha 1 and NK-beta 1 subunit protein expression and Na,K-ATPase activity increased. The magnitude of Na,K-ATPase-mediated NH<UP><SUB>4</SUB><SUP>+</SUP></UP> uptake across the basolateral membrane (J<SUB>NH<SUP>+</SUP><SUB>4</SUB></SUB>) was determined in tIMCD tubules perfused in vitro from rats after 3 days of a normal or a K+-restricted diet. J<SUB>NH<SUP>+</SUP><SUB>4</SUB></SUB> was the same in tubules from rats on either diet when measured at the same extracellular K+ concentration. However, in either treatment group, increasing K+ concentration from 10 to 30 mM reduced J<SUB>NH<SUP>+</SUP><SUB>4</SUB></SUB> >60%. In conclusion, with 3 days of K+ restriction, NH<UP><SUB>4</SUB><SUP>+</SUP></UP> uptake by Na,K-ATPase is increased in the tIMCD primarily from the reduced interstitial K+ concentration.

sodium,hydrogen-adenosinetriphosphatase; terminal inner medullary collecting duct; potassium; ammonium


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