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EDITORIAL FOCUS

Angiotensin II increases chloride absorption in the cortical collecting duct in mice through a pendrin-dependent mechanism

¹Renal Division, Department of Medicine, and ⁴Department of Physiology, Emory University School of Medicine, Atlanta, Georgia; ²Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York; ³The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom

Submitted 8 September 2006 ; accepted in final form 13 October 2006

Pendrin (Slc26a4) localizes to type B and non-A, non-B intercalated cells in the distal convoluted tubule, the connecting tubule, and the cortical collecting duct (CCD), where it mediates apical Cl^–/HCO₃^– exchange. The purpose of this study was to determine whether angiotensin II increases transepithelial net chloride transport, J_Cl, in mouse CCD through a pendrin-dependent mechanism. J_Cl and transepithelial voltage, V_T, were measured in CCDs perfused in vitro from wild-type and Slc26a4 null mice ingesting a NaCl-replete diet or a NaCl-replete diet and furosemide. In CCDs from wild-type mice ingesting a NaCl-replete diet, V_T and J_Cl were not different from zero either in the presence or absence of angiotensin II (10^–8 M) in the bath. Thus further experiments employed mice given the high-NaCl diet and furosemide to upregulate renal pendrin expression. CCDs from furosemide-treated wild-type mice had a lumen-negative V_T and absorbed Cl^–. With angiotensin II in the bath, Cl^– absorption doubled although V_T did not become more lumen negative. In contrast, in CCDs from furosemide-treated Slc26a4 null mice, Cl^– secretion and a V_T of 0 were observed, neither of which changed with angiotensin II application. Inhibiting ENaC with benzamil abolished V_T although J_Cl fell only 50%. Thus substantial Cl^– absorption is observed in the absence of an electromotive force. Attenuating apical anion exchange with the peritubular application of the H⁺-ATPase inhibitor bafilomycin abolished benzamil-insensitive Cl^– absorption. In conclusion, angiotensin II increases transcellular Cl^– absorption in the CCD through a pendrin- and H⁺-ATPase-dependent process.

transepithelial voltage; bafilomycin; H⁺-ATPase; knockout mice; S1c26a4; intercalated cell

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