Increased CO(2) stimulates K/Rb reabsorption mediated by H-K-ATPase in CCD of potassium-restricted rabbit

• Published in: American journal of physiology. Renal physiology 2001-08, Vol.281 (2), p.F366-F373
• Main Authors: Zhou, X, Nakamura, S, Xia, S L, Wingo, C S
• Format: Article
• Language: English
• Subjects: Absorption; Animals; Carbon Dioxide - metabolism; Chelating Agents - pharmacology; Colchicine - pharmacology; Diuretics - pharmacology; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Enzyme Inhibitors - pharmacology; Female; Gout Suppressants - pharmacology; H(+)-K(+)-Exchanging ATPase - metabolism; Imidazoles - pharmacology; In Vitro Techniques; Kidney Tubules, Collecting - drug effects; Kidney Tubules, Collecting - metabolism; Methazolamide - pharmacology; Perfusion; Potassium - metabolism; Proton Pump Inhibitors; Rabbits; Rubidium - metabolism; Sulfonamides - pharmacology
• ISSN: 1931-857X
• DOI: 10.1152/ajprenal.2001.281.2.F366

Apical H-K-ATPase in the cortical collecting duct (CCD) plays an important role in urinary acidification and K reabsorption. Our previous studies demonstrated that an H-K-ATPase mediates, in part, Rb reabsorption in rabbit CCD (Zhou X and Wingo CS. Am J Physiol Renal Fluid Electrolyte Physiol 263: F1134-F1141, 1992). The purpose of these experiments was to examine using in vitro microperfused CCD from K-restricted rabbits 1) whether an acute increase in PCO(2) and, presumably, intracellular acidosis stimulate K absorptive flux; and 2) whether this stimulation was dependent on the presence of a functional H-K-ATPase. Rb reabsorption was significantly increased after exposure to 10% CO(2) in CCD, and this effect was persistent for the entire 10% CO(2) period, whereas 10 microM SCH-28080 in the perfusate totally abolished the stimulation of Rb reabsorption by 10% CO(2). After stimulation of Rb reabsorption by 10% CO(2), subsequent addition of 0.1 mM methazolamide, an inhibitor of carbonic anhydrase, failed to affect Rb reabsorption. However, simultaneous exposure to 10% CO(2) and methazolamide prevented the stimulation of Rb reabsorption. Treatment with the intracellular calcium chelator MAPTAM (0.5 microM) inhibited the stimulation of Rb reabsorption by 10% CO(2). Similar inhibition was also observed in the presence of either a calmodulin inhibitor, W-7 (0.5 microM), or colchicine (0.5 mM), an inhibitor of tubulin polymerization. In time control studies, the perfusion time did not significantly affect Rb reabsorption. We conclude the following: 1) stimulation of Rb reabsorption on exposure to 10% CO(2) is dependent on the presence of a functional H-K-ATPase and appears to be regulated in part by the insertion of this enzyme into the apical plasma membrane by exocytosis; 2) insertion of H-K-ATPase requires changes in intracellular pH and needs a basal level of intracellular calcium concentration; and 3) H-K-ATPase insertion occurs by a microtubule-dependent process.