Kurtz I, Petrasek D, Tatishchev S
Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1689, USA.
J Membr Biol. 2004 Jan 15;197(2):77-90. doi: 10.1007/s00232-003-0643-x.
The electrogenic Na(+)-HCO(3)(-) cotransporters play an essential role in regulating intracellular pH and extracellular acid-base homeostasis. Of the known members of the bicarbonate transporter superfamily (BTS), NBC1 and NBC4 proteins have been shown to be electrogenic. The electrogenic nature of these transporters results from the unequal coupling of anionic and cationic fluxes during each transport cycle. This unique property distinguishes NBC1 and NBC4 proteins from other sodium bicarbonate cotransporters and members of the bicarbonate transporter superfamily that are known to be electroneutral. Structure-function studies have played an essential role in revealing the basis for the modulation of the coupling ratio of NBC1 proteins. In addition, the recent transmembrane topographic analysis of pNBC1 has shed light on the potential structural determinants that are responsible for ion permeation through the cotransporter. The experimentally difficult problem of determining the nature of anionic species being transported by these proteins (HCO(3)(-) versus CO(3)(2-)) is analyzed using a theoretical equilibrium thermodynamics approach. Finally, our current understanding of the molecular mechanisms responsible for the regulation of ion coupling and flux through electrogenic sodium bicarbonate cotransporters is reviewed in detail.
电生性钠-碳酸氢根共转运体在调节细胞内pH值和细胞外酸碱平衡中起着至关重要的作用。在已知的碳酸氢根转运体超家族(BTS)成员中,NBC1和NBC4蛋白已被证明具有电生性。这些转运体的电生性源于每个转运循环中阴离子和阳离子通量的不等量偶联。这种独特的特性将NBC1和NBC4蛋白与其他已知为电中性的钠碳酸氢根共转运体以及碳酸氢根转运体超家族成员区分开来。结构-功能研究在揭示NBC1蛋白偶联比率调节的基础方面发挥了重要作用。此外,最近对pNBC1的跨膜拓扑分析揭示了负责离子通过共转运体渗透的潜在结构决定因素。使用理论平衡热力学方法分析了确定这些蛋白转运的阴离子种类性质(碳酸氢根对碳酸根)这一实验上困难的问题。最后,详细综述了我们目前对负责调节离子偶联和通过电生性钠碳酸氢根共转运体通量的分子机制的理解。