K-DEPLETION MODIFIES THE PROPERTIES OF SCH-28080-SENSITIVE K-ATPASE IN RAT COLLECTING DUCT

Two distinct Sch-28080-sensitive K-adenosinetriphosphatases (K-ATPases ) were previously described in the rat nephron: a ouabain-resistant K- ATPase (type I) present in collecting ducts (CD) and a ouabain-sensiti ve form (type II) located in proximal tubules (PT) and thick ascending limbs (TAL). In K-depleted rats, K-ATPase activity is increased in CD , whereas it is reduced in PT and TAL. Because expression of colonic H -K-ATPase is restricted to the CD of K-depleted rats, we hypothesized that K-ATPase from the CD of K-depleted rats might be different from t ypes I and II. Indeed, type III K-ATPase displays higher sensitivities to ouabain and to Sch-28080 than type II, a lower sensitivity to Sch- 28080 than type I, and, conversely to types I and II, it can be stimul ated by Na+. Pharmacological differences between types II and III K-AT Pases were confirmed by [H-3]ouabain binding experiments. Thus the rat kidney expresses three K-ATPases that differ by their pharmacological and kinetic properties, their distribution profile along the nephron, and their behavior during K depletion.