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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/F621    most recent 00412.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lynch, I. J. Articles by Wingo, C. S. Search for Related Content PubMed PubMed Citation Articles by Lynch, I. J. Articles by Wingo, C. S.

Impaired acid secretion in cortical collecting duct intercalated cells from H-K-ATPase-deficient mice: role of HK isoforms

¹North Florida/South Georgia Veterans Health System and ²College of Medicine, University of Florida, Gainesville, Florida; and ³College of Medicine, University of Cincinnati, Cincinnati, Ohio

Submitted 5 September 2007 ; accepted in final form 5 December 2007

Two classes of H pumps, H-K-ATPase and H-ATPase, contribute to luminal acidification and HCO₃ transport in the collecting duct (CD). At least two H-K-ATPase -subunits are expressed in the CD: HK₁ and HK₂. Both exhibit K dependence but have different inhibitor sensitivities. The HK₁ H-K-ATPase is Sch-28080 sensitive, whereas the pharmacological profile of the HK₂ H-K-ATPase is not completely understood. The present study used a nonpharmacological, genetic approach to determine the contribution of HK₁ and HK₂ to cortical CD (CCD) intercalated cell (IC) proton transport in mice fed a normal diet. Intracellular pH (pH_i) recovery was determined in ICs using in vitro microperfusion of CCD after an acute intracellular acid load in wild-type mice and mice of the same strain lacking expression of HK₁, HK₂, or both H-K-ATPases (HK_1,2). A-type and B-type ICs were differentiated by luminal loading with BCECF-AM and peritubular chloride removal from CO₂/HCO₃-buffered solutions to identify the membrane locations of Cl/HCO₃ exchange activity. H-ATPase- and Na/H exchange-mediated H transport were inhibited with bafilomycin A₁ (100 nM) and EIPA (10 µM), respectively. Here, we report 1) initial pH_i and buffering capacity were not significantly altered in the ICs of HK-deficient mice, 2) either HK₁ or HK₂ deficiency resulted in slower acid extrusion, and 3) A-type ICs from HK_1,2-deficient mice had significantly slower acid extrusion compared with A-type ICs from HK₁-deficient mice alone. These studies are the first nonpharmacological demonstration that both HK₁ and HK₂ contribute to H secretion in both A-type and B-type ICs in animals fed a normal diet.

potassium; microperfusion; pH; acid-base balance; P-type ATPase

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