Na+/HCO3- Cotransporter NBCn2 Mediates HCO3- Reclamation in the Apical Membrane of Renal Proximal Tubules
Na+/HCO3- Cotransporter NBCn2 Mediates HCO3- Reclamation in the Apical Membrane of Renal Proximal Tubules
复制标题
Na /HCO3- 协同转运蛋白 NBCn2 介导肾近端小管顶膜中的 HCO3- 回收
DOI：
10.1681/asn.2016080930
复制
发表时间：
2017-08-01
影响因子：
13.6
通讯作者：
Chen, Li-Ming
中科院分区：
文献类型：
--
作者：
Guo, Yi-Min;Liu, Ying;Chen, Li-Ming
肾脏通过从肾小管腔回收几乎所有肾小球中过滤的HCO 3和分泌额外的H+来滴定管腔来维持全身酸碱平衡。缓冲器。对于近端小管，这是负责约80%的这种活动，据信，HCO 3-回收仅取决于H+分泌，介导的顶端Na+/H+交换NHE 3和液泡质子泵。然而，NHE 3和质子泵不能解释所有的HCO 3-回收。在这里，我们研究了两种变体的电中性Na+/HCO 3-协同转运蛋白NBCn 2的潜在贡献，其氨基末端以氨基酸MCDL（MCDL-NBCn 2）和MEIK（MEIK-NBCn 2）开始。免疫印迹分析和免疫细胞化学显示，MEIK-NBCn 2主要定位于大鼠肾脏髓质厚升支的基底外侧膜，而MCDL-NBCn 2定位于近端小管的顶膜。值得注意的是，NH 4Cl诱导的全身代谢性酸中毒或低钾性碱中毒下调MCDL-NBCn 2的丰度，并相反上调NHE 3。相反，NaHCO 3诱导的代谢性纤维化上调MCDL-NBCn 2和NHE 3下调。我们建议，近端小管的顶膜有两种不同的策略HCO 3-回收：传统的间接途径，其中v和质子泵分泌H+滴定管腔HCO 3-，和新的直接途径，其中NBCn 2从管腔中除去HCO 3-。NBCn 2和NHE 3在不同生理条件下的相互调节与我们的数学模拟一致，这表明HCO 3-摄取和H+分泌具有HCO 3-回收与鲁米诺滴定的相互效率。缓冲器。
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.