期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 28, 期 8, 页码 2409-2419出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2016080930
关键词
-
资金
- Meyers/Scarpa Chair
- National Science Foundation of China [31371171, 81571388, 31571201]
- Fundamental Research Funds for the Central Universities of China [2016YXMS263]
- National Institutes of Health [U01-GM111251, K01-DK107787]
- Office of Naval Research [N00014-15-1-2060]
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 lumina! 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 v 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 lumina! buffers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据