Aronson P S
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Wien Klin Wochenschr. 1997 Jun 27;109(12-13):435-40.
We have studied the mechanisms of NaCl transport in the mammalian proximal tubule. We identified Cl(-)-formate and Cl(-)-oxalate exchangers as possible mechanism's of uphill Cl- entry across the apical membrane of proximal tubule cells. For steady state Cl- absorption to occur by these mechanisms, formate and oxalate must recycle from lumen to cell. Recycling of formate from lumen to cell may occur by H(+)-coupled formate transport and nonionic diffusion of formic acid in parallel with Na(+)-H+ exchange. Oxalate recycling from lumen to cell may take place by oxalate-sulfate exchange in parallel with Na(+)-sulfate cotransport. Cl- exit across the basolateral membrane is most likely mediated by Cl- channels. To identify the Na(+)-H+ exchanger (NHE) isoform(s) expressed on the brush border membrane of proximal tubule cells, we developed isoform-specific monoclonal and polyclonal antibodies. We found that NHE1 is present on the basolateral membrane of all nephron segments, whereas NHE3 is present on the apical membrane of cells in the proximal tubule and the thin and thick limbs of the loop of Henle. NHE3 is also present in a population of subapical intracellular vesicles, suggesting possible regulation by membrane trafficking. The inhibitor sensitivity of Na(+)-H+ exchange in renal brush border vesicles indicates that it is mediated by NHE3 under baseline conditions and during up-regulation by metabolic acidosis. Increased apical membrane Na(+)-H+ exchange activity in response to metabolic acidosis and during renal maturation is associated with increased NHE3 protein expression. Finally, we found that the organic anion-dependent absorption of Cl- is markedly down-regulated in metabolic acidosis in parallel with the up-regulation of brush border membrane Na(+)-H+ exchange. Thus, differential regulation of apical membrane ion exchangers may provide a mechanism to regulate the relative rates of NaHCO3 and NaCl reabsorption.
我们研究了哺乳动物近端小管中氯化钠转运的机制。我们确定了氯离子 - 甲酸根和氯离子 - 草酸根交换体，它们可能是氯离子跨近端小管细胞顶端膜进行主动转运的机制。要通过这些机制实现氯离子的稳态吸收，甲酸根和草酸根必须从管腔循环至细胞内。甲酸根从管腔循环至细胞内可能通过氢离子偶联的甲酸根转运以及甲酸的非离子扩散与钠离子 - 氢离子交换并行发生。草酸根从管腔循环至细胞内可能通过草酸根 - 硫酸根交换与钠离子 - 硫酸根共转运并行发生。氯离子跨基底外侧膜的排出很可能是由氯离子通道介导的。为了鉴定近端小管细胞刷状缘膜上表达的钠离子 - 氢离子交换体（NHE）亚型，我们制备了亚型特异性的单克隆和多克隆抗体。我们发现NHE1存在于所有肾单位节段的基底外侧膜上，而NHE3存在于近端小管以及髓袢细段和粗段细胞的顶端膜上。NHE3也存在于一群顶端下的细胞内小泡中，提示可能受膜运输调控。肾刷状缘小泡中钠离子 - 氢离子交换的抑制剂敏感性表明，在基础条件下以及代谢性酸中毒上调过程中，它是由NHE3介导的。代谢性酸中毒和肾脏成熟过程中顶端膜钠离子 - 氢离子交换活性增加与NHE3蛋白表达增加相关。最后，我们发现代谢性酸中毒时，氯离子的有机阴离子依赖性吸收显著下调，同时刷状缘膜钠离子 - 氢离子交换上调。因此，顶端膜离子交换体的差异调节可能为调节碳酸氢钠和氯化钠重吸收的相对速率提供一种机制。
