Gadea A, López-Colomé A M
Instituto e Fisiología Celular, Departamento de Neurociencias, UNAM, Mexico.
J Neurosci Res. 2001 Mar 15;63(6):453-60. doi: 10.1002/jnr.1039.
The termination of chemical neurotransmission in the CNS involves the rapid removal of neurotransmitter from synapses by specific transport systems. Such mechanism operates for the three major amino acid neurotransmitters glutamate, gamma-aminobutyric acid (GABA) and glycine. To date, five different high-affinity Na(+)-dependent glutamate (Glu) transporters have been cloned: GLT1, GLAST, EAAC1, EAAT4 and EAAT5. The first two are expressed mainly by glial cells, and seem to be the predominant Glu transporters in the brain. A major function of Glu uptake in the nervous system is to prevent extracellular Glu concentrations from raising to neurotoxic levels in which glial transporters seem to play a critical role in protecting neurons from glutamate-induced excitotoxicity. Under particular conditions, glial GluTs have been shown to release Glu by reversal of activity, in a Ca(2+)--and energy-independent fashion. Furthermore, an activity of these transporters as ion channels or transducing units coupled to G-proteins has recently been reported. The localization, stoichiometry, and regulation of glial GluTs are outlined, as well as their possible contributions to nervous system diseases as ALS, AD and ischemic damage.
中枢神经系统中化学神经传递的终止涉及通过特定转运系统快速从突触中清除神经递质。这种机制作用于三种主要的氨基酸神经递质，即谷氨酸、γ-氨基丁酸（GABA）和甘氨酸。迄今为止，已克隆出五种不同的高亲和力钠依赖性谷氨酸（Glu）转运体：GLT1、GLAST、EAAC1、EAAT4和EAAT5。前两种主要由神经胶质细胞表达，似乎是大脑中主要的Glu转运体。神经系统中Glu摄取的一个主要功能是防止细胞外Glu浓度升高到神经毒性水平，在这方面神经胶质转运体似乎在保护神经元免受谷氨酸诱导的兴奋毒性中起关键作用。在特定条件下，已证明神经胶质Glu转运体可通过活性逆转以不依赖钙和能量的方式释放Glu。此外，最近有报道称这些转运体具有作为离子通道或与G蛋白偶联的转导单元的活性。概述了神经胶质Glu转运体的定位、化学计量和调节，以及它们对诸如肌萎缩侧索硬化症、阿尔茨海默病和缺血性损伤等神经系统疾病可能产生的影响。
