RGD Reference Report - Na+/HCO3- Cotransporter NBCn2 Mediates HCO3- Reclamation in the Apical Membrane of Renal Proximal Tubules. - Rat Genome Database

RGD Reference Report - Na+/HCO3- Cotransporter NBCn2 Mediates HCO3- Reclamation in the Apical Membrane of Renal Proximal Tubules. - Rat Genome Database

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Na+/HCO3- Cotransporter NBCn2 Mediates HCO3- Reclamation in the Apical Membrane of Renal Proximal Tubules.
Authors:	Guo, Yi-Min Liu, Ying Liu, Mei Wang, Jin-Lin Xie, Zhang-Dong Chen, Kang-Jing Wang, Deng-Ke Occhipinti, Rossana Boron, Walter F Chen, Li-Ming
Citation:	Guo YM, etal., J Am Soc Nephrol. 2017 Aug;28(8):2409-2419. doi: 10.1681/ASN.2016080930. Epub 2017 Mar 9.
RGD ID:	14397576
Pubmed:	PMID:28280139 (View Abstract at PubMed)
PMCID:	PMC5533233 (View Article at PubMed Central)
DOI:	DOI:10.1681/ASN.2016080930 (Journal Full-text)
The kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO3- filtered in glomeruli and by secreting additional H+ to titrate luminal buffers. For proximal tubules, which are responsible for about 80% of this activity, it is believed that HCO3- reclamation depends solely on H+ secretion, mediated by the apical Na+/H+ exchanger NHE3 and the vacuolar proton pump. However, NHE3 and the proton pump cannot account for all HCO3- reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na+/HCO3- cotransporter NBCn2, the amino termini of which start with the amino acids MCDL (MCDL-NBCn2) and MEIK (MEIK-NBCn2). Western blot analysis and immunocytochemistry revealed that MEIK-NBCn2 predominantly localizes at the basolateral membrane of medullary thick ascending limbs in the rat kidney, whereas MCDL-NBCn2 localizes at the apical membrane of proximal tubules. Notably, NH4Cl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE3 Conversely, NaHCO3-induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE3 We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO3- reclamation: the conventional indirect pathway, in which NHE3 and the proton pump secrete H+ to titrate luminal HCO3-, and the novel direct pathway, in which NBCn2 removes HCO3- from the lumen. The reciprocal regulation of NBCn2 and NHE3 under different physiologic conditions is consistent with our mathematical simulations, which suggest that HCO3- uptake and H+ secretion have reciprocal efficiencies for HCO3- reclamation versus titration of luminal buffers.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Slc4a10	Rat	apical plasma membrane	located_in	IDA		PMID:28280139	UniProt
Slc4a10	Rat	basolateral plasma membrane	located_in	IDA		PMID:28280139	UniProt

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Genes (Rattus norvegicus)

Slc4a10 (solute carrier family 4 member 10)

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