Deficient acid handling with distal RTA in the NBCe2 knockout mouse.

Deficient acid handling with distal RTA in the NBCe2 knockout mouse. Am J Physiol Renal Physiol. 2015 Jun 24;:ajprenal.00163.2015 Authors: Wen D, Yuan Y, Cornelius RJ, Li H, Warner PC, Wang B, Wang-France J, Boettger T, Sansom SC 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- co-transporter NBCe2/Slc4a5 (NBCe2-KO) developed dRTA after an oral acid challenge. NBCe2 expression was identified in the connecting tubule (CNT) of wild type mice (WT), and its expression was significantly increased after acid loading. NBCe2-KO did not have dRTA when on a standard mouse diet. However, after acid loading, NBCe2-KO exhibited complete features of dRTA, characterized by insufficient urinary acidification, hyperchloremic hypokalemic metabolic acidosis, and hypercalciuria. Additional experiments showed that NBCe2-KO had decreased luminal trans-epithelial voltage (Vte) in the CNT as revealed by micro-puncture. Further immunofluorescence and Western blot experiments found NBCe2-KO had increased expression of H+-ATPase B1 in the plasma membrane. These results showed that NBCe2-KO with acid loading developed increased urinary K+ and Ca2+ wasting due to the decreased luminal Vte in the CNT. NBCe2-KO compensated to maintain systemic pH by increasing H+-ATPase in the plasma membrane. Therefore, defects in NBCe2 ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research