Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Donghai Wen, Yang Yuan, Ryan J. Cornelius, Huaqing Li, Paige C. Warner, Bangchen Wang, Jun Wang-France, Thomas Boettger, Steven C. Sansom

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 Ca2+ 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 Ca2+ in the distal nephron.

Original languageEnglish (US)
Pages (from-to)F523-F530
JournalAmerican Journal of Physiology - Renal Physiology
Volume309
Issue number6
DOIs
StatePublished - Sep 15 2015

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Keywords

  • Connecting tubule
  • Distal renal tubular acidosis
  • Electrogenic Na<sup>+</sup>-HCO<inf>3</inf><sup>-</sup> cotransporter

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Wen, D., Yuan, Y., Cornelius, R. J., Li, H., Warner, P. C., Wang, B., Wang-France, J., Boettger, T., & Sansom, S. C. (2015). Deficient acid handling with distal RTA in the NBCe2 knockout mouse. American Journal of Physiology - Renal Physiology, 309(6), F523-F530. https://doi.org/10.1152/ajprenal.00163.2015