Na+/HCO3 – Cotransporter NBCn2 Mediates HCO3 − Reclamation in the Apical Membrane of Renal Proximal Tubules

作者：Yimin Guo, Ying Liu, Mei Liu, Jin-Lin Wang, Zhang-Dong Xie, Kang-Jing Chen, Deng-Ke Wang, Rossana Occhipinti, Walter F. Boron, Liming Chen · 发表于：Journal of the American Society of Nephrology · 年份：2017 · DOI：10.1681/asn.2016080930 · 被引用次数：34 · 研究领域：Ion Transport and Channel Regulation、Renal function and acid-base balance、Ion channel regulation and function

The kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO 3 − 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 HCO 3 − reclamation depends solely on H + secretion, mediated by the apical Na + /H + exchanger NHE 3 and the vacuolar proton pump. However, NHE3 and the proton pump cannot account for all HCO 3 − reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na + /HCO 3 – 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, NH 4 Cl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE 3 . Conversely, NaHCO 3 -induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE 3 . We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO 3 − reclamation: the conventional indirect pathway, in which NHE 3 and the proton pump secrete H + to titrate luminal HCO 3 − , and the novel direct pathway, in which NB...