Felder Robin A, Jose Pedro A, Xu Peng, Gildea John J
Department of Pathology, The University of Virginia, Charlottesville, VA, 22903, USA.
Department of Medicine, Division of Renal Diseases and Hypertension and Department of Pharmacology and Physiology, The George Washington University, Washington, DC, 20057, USA.
Curr Hypertens Rep. 2016 Sep;18(9):71. doi: 10.1007/s11906-016-0679-9.
The sodium bicarbonate cotransporter (NBCe2, aka NBC4) was originally isolated from the human testis and heart (Pushkin et al. IUBMB Life 50:13-19, 2000). Subsequently, NBCe2 was found in diverse locations where it plays a role in regulating sodium and bicarbonate transport, influencing intracellular, extracellular, interstitial, and ultimately plasma pH (Boron et al. J Exp Biol. 212:1697-1706, 2009; Parker and Boron, Physiol Rev. 93:803-959, 2013; Romero et al. Mol Asp Med. 34:159-182, 2013). NBCe2 is located in human and rodent renal-collecting duct and proximal tubule. While much is known about the two electrogenic sodium bicarbonate cotransporters, NBCe1 and NBCe2, in the regulation of sodium homeostasis and pH balance in the rodent kidney, little is known about their roles in human renal physiology. NBCe2 is located in the proximal tubule Golgi apparatus under basal conditions and then disperses throughout the cell, but particularly into the apical membrane microvilli, during various maneuvers that increase intracellular sodium. This review will summarize our current understanding of the distribution and function of NBCe2 in the human kidney and how genetic variants of its gene, SLC4A5, contribute to salt sensitivity of blood pressure.
碳酸氢钠协同转运蛋白（NBCe2，又名NBC4）最初是从人类睾丸和心脏中分离出来的（普希金等人，《国际生物化学与分子生物学联盟生活》50:13 - 19，2000年）。随后，在不同部位发现了NBCe2，它在调节钠和碳酸氢盐转运中发挥作用，影响细胞内、细胞外、间质以及最终的血浆pH值（博龙等人，《实验生物学杂志》212:1697 - 1706，2009年；帕克和博龙，《生理学评论》93:803 - 959，2013年；罗梅罗等人，《分子医学展望》34:159 - 182，2013年）。NBCe2位于人类和啮齿动物的肾集合管和近端小管中。虽然人们对两种电生性碳酸氢钠协同转运蛋白NBCe1和NBCe2在啮齿动物肾脏钠稳态和pH平衡调节方面了解很多，但对它们在人类肾脏生理学中的作用却知之甚少。在基础条件下，NBCe2位于近端小管高尔基体中，然后在各种增加细胞内钠的操作过程中分散到整个细胞中，但尤其会分散到顶端膜微绒毛中。本综述将总结我们目前对NBCe2在人类肾脏中的分布和功能的理解，以及其基因SLC4A5的遗传变异如何导致血压的盐敏感性。
