Na+/HCO3– Cotransporter NBCn2 Mediates HCO3− Reclamation in the Apical Membrane of Renal Proximal Tubules
| Autor: | Ying Liu, Li-Ming Chen, Deng Ke Wang, Rossana Occhipinti, Zhang Dong Xie, Yi Min Guo, Kang Jing Chen, Mei Liu, Jin-Lin Wang, Walter F. Boron |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
inorganic chemicals Metabolic alkalosis Acid–base homeostasis Kidney Rats Sprague-Dawley Kidney Tubules Proximal 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Secretion Epithelial polarity chemistry.chemical_classification Ion Transport urogenital system Sodium-Bicarbonate Symporters Cell Membrane General Medicine Apical membrane medicine.disease Cell biology Amino acid Rats Bicarbonates 030104 developmental biology medicine.anatomical_structure Basic Research Kidney Tubules chemistry Nephrology Cotransporter 030217 neurology & neurosurgery |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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