In rat inner medullary collecting duct, NH 4 + uptake by the Na,K-ATPase is increased during hypokalemia

Abstract

In rat terminal inner medullary collecting duct (tIMCD), the Na,K-ATPase mediates NH[Formula: see text] uptake, which increases secretion of net H+ equivalents. K+ and NH[Formula: see text]compete for a common binding site on the Na,K-ATPase. Therefore, NH[Formula: see text] 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[Formula: see text] 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 β1-subunit (NK-β1) protein expression increased although NK-α1 protein expression and Na,K-ATPase activity were unchanged relative to K+-replete controls. However, after 7 days of K+ restriction, both NK-α1 and NK-β1 subunit protein expression and Na,K-ATPase activity increased. The magnitude of Na,K-ATPase-mediated NH[Formula: see text]uptake across the basolateral membrane ( J [Formula: see text]) was determined in tIMCD tubules perfused in vitro from rats after 3 days of a normal or a K+-restricted diet. J [Formula: see text] 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 [Formula: see text] >60%. In conclusion, with 3 days of K+ restriction, NH[Formula: see text] uptake by Na,K-ATPase is increased in the tIMCD primarily from the reduced interstitial K+ concentration.