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Deficiency in NBCe2 causes distal renal tubular acidosis (891.2)
Author(s) -
Wen Donghai,
Cornelius Ryan,
Warner Paige,
Boettger Thomas,
Sansom Steven
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.891.2
Subject(s) - distal renal tubular acidosis , intercalated cell , cotransporter , acidosis , intracellular ph , western blot , renal tubular acidosis , chemistry , microbiology and biotechnology , immunohistochemistry , homeostasis , medicine , apical membrane , endocrinology , intracellular , biology , kidney , biochemistry , sodium , membrane , organic chemistry , gene
The pathogenesis of distal renal tubular acidosis (dRTA) is not fully understood. Here we show that the electrogenic Na/HCO3 cotransporter NBCe2 is involved in the pathophysiology of dRTA by reabsorbing HCO3 in the collecting duct (CD). NBCe2 knockout (KO) and wild type (WT) mice were fed with acid water for 7‐10 days and placed in metabolic cages. Immunohistochemistry (IHC) and Western blot were used to examine the expressions of NBCe2 and H‐ATPase B1 in the kidneys. IHC showed NBCe2 was expressed mostly at the apical membrane of Type A intercalated cells (α‐IC) of the CD. The H‐ATPase B1 expression was higher in the plasma membrane of α‐IC in NBCe2 KO than WT, suggesting compensation for NBCe2 defect. As compared with WT, NBCe2‐KO exhibited significantly lower plasma pH, [HCO3] and [K], while the urine pH, K clearance and transtubular K gradient were increased. NBCe2 expression was also examined in cultured MDCK‐C11 cells by immunocytochemistry (ICC), which showed that NBCe2 was expressed selectively at the apical membrane in C11 cells. The intracellular pH (pHi) recovery rate in C11 cells was recorded using BCECF. Knocking down of NBCe2 expression by siRNA significantly decreased the pHi recovery rate in C11 cells. In conclusion, NBCe2 plays an important role in reabsorbing HCO3 in the CD. NBCe2 deficiency leads to hypokalemic acidosis and is another form of dRTA. Grant Funding Source : NIDDK