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Na+/HCO3−共转运体NBCe1的生理及病理学作用

刘 颖, 卢群伟, 陈历明

华中科技大学生命科学与技术学院生物物理学及分子生理学系；遗传与发育生物学系；分子生物物理学教育部重点实验室，武汉 430074

摘要

维持机体的酸碱稳态对各项生理活动的有序进行具有根本性的意义，酸碱紊乱会导致一系列疾病。碳酸氢根(HCO3−)是机体中最重要的酸碱缓冲离子。SLC4家族的HCO3−跨膜转运体是机体最主要的HCO3−跨膜运输载体之一，在细胞的pH调控以及上皮细胞中HCO3−的吸收或分泌过程中起着非常重要的作用。SLC4家族的NBCe1(SLC4A4)是一个生电型的Na+/HCO3−共转运体，在各种组织中有着非常广泛的表达，具有极其重要的生理学作用。在肾脏近端肾小管中，NBCe1负责80%以上的HCO3−的重吸收，对于维持机体全局的酸碱平衡极其重要。人类的SLC4A4突变常导致严重的近端肾小管性酸中毒，且常伴有侏儒症、偏头疼、白内障、青光眼以及牙齿釉质发育异常等。本文对最近十多年来有关NBCe1的结构-功能关系、功能调控机制、NBCe1的生理及病理学作用机理等方面的研究进展进行综述与分析。

关键词： 碳酸氢根转运体; 酸碱平衡调控; 肾小管; 偏头疼; 代谢性酸中毒; SLC4A4

[Physiology and pathophysiology of Na(+)/HCO3(-) cotransporter NBCe1.] [Article in Chinese]

LIU Ying, LU QunWei, CHEN LiMing

Department of Biophysics and Molecular Physiology； Department of Genetics and Developmental Biology； Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Abstract

Na(+)/HCO3(-) cotransporter NBCe1 is an electrogenic member of the solute carrier 4 (SLC4) family and plays important roles in intracellular pH regulation as well as transepithelial HCO3(-) movement. The physiological and pathological significance of NBCe1 has been well established by genetic studies with humans as well as knock-out study with mouse. NBCe1 is expressed in diverse tissues in mammals. The transporter plays an essential role in the maintenance of acid-base homeostasis in our body, being responsible for more ~80% of HCO3(-) reabsorption in the proximal renal tubule. In humans, a number of SLC4A4 mutations have been associated with proximal renal tubule acidosis that is often accompanied with short stature, ocular abnormalities (including cataract, glaucoma, and band keratopathy), migraine, and/or defects in dental enamel development. In the present article, we review the molecular physiology, the structure/function relationship, the mechanisms underlying the functional regulation of NBCe1, as well as the physiological and pathological roles of the transporter.

Key words: bicarbonate transporter; acid-base balance; renal tubule; migraine; metabolic acidosis; SLC4A4

收稿日期：2012-03-11　　录用日期：2012-05-30

通讯作者：陈历明　　E-mail: liming.chen@mail.hust.edu.cn

引用本文：

刘 颖, 卢群伟, 陈历明. Na+/HCO3−共转运体NBCe1的生理及病理学作用[J]. 生理学报 2012; 64 (6): 729-740.

LIU Ying, LU QunWei, CHEN LiMing. [Physiology and pathophysiology of Na(+)/HCO3(-) cotransporter NBCe1.] [Article in Chinese] . Acta Physiol Sin 2012; 64 (6): 729-740 (in Chinese with English abstract).