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脑脊液生成的分子机制。

Molecular mechanisms of cerebrospinal fluid production.

作者信息

Brown P D, Davies S L, Speake T, Millar I D

机构信息

School of Biological Sciences, G.38 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.

出版信息

Neuroscience. 2004;129(4):957-70. doi: 10.1016/j.neuroscience.2004.07.003.

Abstract

The epithelial cells of the choroid plexuses secrete cerebrospinal fluid (CSF), by a process which involves the transport of Na(+), Cl(-) and HCO(3)(-) from the blood to the ventricles of the brain. The unidirectional transport of ions is achieved due to the polarity of the epithelium, i.e. the ion transport proteins in the blood-facing (basolateral) membrane are different to those in the ventricular (apical) membrane. The movement of ions creates an osmotic gradient which drives the secretion of H(2)O. A variety of methods (e.g. isotope flux studies, electrophysiological, RT-PCR, in situ hybridization and immunocytochemistry) have been used to determine the expression of ion transporters and channels in the choroid plexus epithelium. Most of these transporters have now been localized to specific membranes. For example, Na(+)-K(+)ATPase, K(+) channels and Na(+)-2Cl(-)-K(+) cotransporters are expressed in the apical membrane. By contrast the basolateral membrane contains Cl(-)- HCO(3) exchangers, a variety of Na(+) coupled HCO(3)(-) transporters and K(+)-Cl(-) cotransporters. Aquaporin 1 mediates water transport at the apical membrane, but the route across the basolateral membrane is unknown. A model of CSF secretion by the mammalian choroid plexus is proposed which accommodates these proteins. The model also explains the mechanisms by which K(+) is transported from the CSF to the blood.

摘要

脉络丛的上皮细胞通过一个涉及将Na(+)、Cl(-)和HCO(3)(-)从血液转运至脑室的过程来分泌脑脊液(CSF)。由于上皮细胞的极性,离子实现单向转运,即面向血液的(基底外侧)膜中的离子转运蛋白与脑室(顶端)膜中的不同。离子的移动产生渗透梯度,驱动H(2)O的分泌。已经使用了多种方法(如同位素通量研究、电生理学、逆转录聚合酶链反应、原位杂交和免疫细胞化学)来确定脉络丛上皮中离子转运体和通道的表达。现在,这些转运体中的大多数已定位到特定的膜上。例如,Na(+)-K(+)ATP酶、K(+)通道和Na(+)-2Cl(-)-K(+)协同转运体在顶端膜中表达。相比之下,基底外侧膜含有Cl(-)-HCO(3)交换体、多种与Na(+)偶联的HCO(3)(-)转运体和K(+)-Cl(-)协同转运体。水通道蛋白1介导顶端膜处的水转运,但穿过基底外侧膜的途径尚不清楚。提出了一个哺乳动物脉络丛分泌脑脊液的模型,该模型纳入了这些蛋白质。该模型还解释了K(+)从脑脊液转运至血液的机制。

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