Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723908.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Deficient acid handling with distal RTA in the NBCe2 knockout mouse
Authors:Wen, D.; Yuan, Y.; Cornelius, R. J.; Li, H.; Warner, P. C.; Wang, B.; Wang-France, J.; Boettger, T.; Sansom, S. C.
Date of Publication (YYYY-MM-DD):2015-09-15
Title of Journal:Am J Physiol Renal Physiol
Volume:309
Issue / Number:6
Start Page:F523
End Page:30
Audience:Not Specified
Abstract / Description:In many circumstances, the pathogenesis of distal renal tubular acidosis (dRTA) is not understood. In the present study, we report that a mouse model lacking the electrogenic Na(+)-HCO3 (-) cotransporter [NBCe2/Slc4a5; NBCe2 knockout (KO) mice] developed dRTA after an oral acid challenge. NBCe2 expression was identified in the connecting tubule (CNT) of wild-type mice, and its expression was significantly increased after acid loading. NBCe2 KO mice did not have dRTA when on a standard mouse diet. However, after acid loading, NBCe2 KO mice exhibited complete features of dRTA, characterized by insufficient urinary acidification, hyperchloremic hypokalemic metabolic acidosis, and hypercalciuria. Additional experiments showed that NBCe2 KO mice had decreased luminal transepithelial potential in the CNT, as revealed by micropuncture. Further immunofluorescence and Western blot experiments found that NBCe2 KO mice had increased expression of H(+)-ATPase B1 in the plasma membrane. These results showed that NBCe2 KO mice with acid loading developed increased urinary K(+) and Ca(2+) wasting due to decreased luminal transepithelial potential in the CNT. NBCe2 KO mice compensated to maintain systemic pH by increasing H(+)-ATPase in the plasma membrane. Therefore, defects in NBCe2 can cause dRTA, and NBCe2 has an important role to regulate urinary acidification and the transport of K(+) and Ca(2+) in the distal nephron.
Free Keywords:Acidosis, Renal Tubular/*metabolism; Animals; Cell Membrane/metabolism; Chlorine/metabolism; Hypercalciuria/metabolism; Hypokalemia/metabolism; Kidney Tubules, Distal/*metabolism; Membrane Proteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Proton-Translocating ATPases/metabolism; Sodium-Bicarbonate Symporters/*genetics/metabolism/*physiology; connecting tubule; distal renal tubular acidosis; electrogenic Na+-HCO3- cotransporter
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. Department of Cellular/Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska; and ssansom@unmc.edu.
Identifiers:ISSN:1522-1466 (Electronic) 1522-1466 (Linking) %R 10.1152/ajprenal.00163.2015
URL:http://www.ncbi.nlm.nih.gov/pubmed/26109087
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.