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EDITORIAL FOCUS
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, JCl, in mouse CCD through a pendrin-dependent mechanism. JCl and transepithelial voltage, VT, 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, VT and JCl were not different from zero either in the presence or absence of angiotensin II (108 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 VT and absorbed Cl. With angiotensin II in the bath, Cl absorption doubled although VT did not become more lumen negative. In contrast, in CCDs from furosemide-treated Slc26a4 null mice, Cl secretion and a VT of
0 were observed, neither of which changed with angiotensin II application. Inhibiting ENaC with benzamil abolished VT although JCl 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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