Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl−/HCO3−exchanger activity and impairs bicarbonate secretion in kidney collecting duct
- 1 July 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 299 (1), C33-C41
- https://doi.org/10.1152/ajpcell.00033.2010
Abstract
The anion exchanger Pendrin, which is encoded by SLC26A4 (human)/Slc26a4 (mouse) gene, is localized on the apical membrane of non-acid-secreting intercalated (IC) cells in the kidney cortical collecting duct (CCD). To examine its role in the mediation of bicarbonate secretion in vivo and the apical Cl−/HCO3−exchanger in the kidney CCD, mice with genetic deletion of pendrin were generated. The mutant mice show the complete absence of pendrin expression in their kidneys as assessed by Northern blot hybridization, Western blot, and immunofluorescence labeling. Pendrin knockout (KO) mice display significantly acidic urine at baseline [pH 5.20 in KO vs. 6.01 in wild type (WT); P < 0.0001] along with elevated serum HCO3−concentration (27.4 vs. 24 meq/l in KO vs. WT, respectively; P < 0.02), consistent with decreased bicarbonate secretion in vivo. The urine chloride excretion was comparable in WT and KO mice. For functional studies, CCDs were microperfused and IC cells were identified by their ability to trap the pH fluorescent dye BCECF. The apical Cl−/HCO3−exchanger activity in B-IC and non-A, non-B-IC cells, as assessed by intracellular pH monitoring, was significantly reduced in pendrin-null mice. The basolateral Cl−/HCO3−exchanger activity in A-IC cells and in non-A, non-B-IC cells, was not different in pendrin KO mice relative to WT animals. Urine NH4+(ammonium) excretion increased significantly, consistent with increased trapping of NH3in the collecting duct in pendrin KO mice. We conclude that Slc26a4 (pendrin) deletion impairs the secretion of bicarbonate in vivo and reduces apical Cl−/HCO3−exchanger activity in B-IC and non-A, non-B-IC cells in CCD. Additional apical Cl−/HCO3−exchanger(s) is (are) present in the CCD.Keywords
This publication has 44 references indexed in Scilit:
- Deletion of the Chloride Transporter Slc26a7 Causes Distal Renal Tubular Acidosis and Impairs Gastric Acid SecretionPublished by Elsevier BV ,2009
- Slc26a9—Anion Exchanger, Channel and Na+ TransporterThe Journal of Membrane Biology, 2009
- Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomachProceedings of the National Academy of Sciences of the United States of America, 2008
- SLC26A9 is a Cl− channel regulated by the WNK kinasesThe Journal of Physiology, 2007
- NaCl Restriction Upregulates Renal Slc26a4 Through Subcellular RedistributionHypertension, 2004
- Deoxycorticosterone Upregulates PDS ( Slc26a4 ) in Mouse KidneyHypertension, 2003
- Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1American Journal of Physiology-Renal Physiology, 2002
- Immunocytochemical localization of pendrin in intercalated cell subtypes in rat and mouse kidneyAmerican Journal of Physiology-Renal Physiology, 2002
- Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS)Nature Genetics, 1997
- Functional characterization of three intercalated cell subtypes in the rabbit outer cortical collecting duct.JCI Insight, 1994