Fairman W A, Vandenberg R J, Arriza J L, Kavanaugh M P, Amara S G
Howard Hughes Medical Institute, Oregon Health Sciences University, Portland 97201, USA.
Nature. 1995 Jun 15;375(6532):599-603. doi: 10.1038/375599a0.
Excitatory amino-acid transporters (EAATs) in the central nervous system maintain extracellular glutamate concentrations below excitotoxic levels and may limit the activation of glutamate receptors. Here we report the cloning of a novel human aspartate/glutamate transporter, EAAT4, which is expressed predominantly in the cerebellum. The transport activity encoded by EAAT4 has high apparent affinity for L-aspartate and L-glutamate, and has a pharmacological profile consistent with previously described cerebellar transport activities. In Xenopus oocytes expressing EAAT4, L-aspartate and L-glutamate elicited a current predominantly carried by chloride ions. This chloride conductance was not blocked by components that block endogenous oocyte chloride channels. Thus EAAT4 combines the re-uptake of neurotransmitter with a mechanism for increasing chloride permeability, both of which could regulate excitatory neurotransmission.
中枢神经系统中的兴奋性氨基酸转运体（EAATs）可将细胞外谷氨酸浓度维持在兴奋性毒性水平以下，并可能限制谷氨酸受体的激活。在此，我们报告了一种新型人类天冬氨酸/谷氨酸转运体EAAT4的克隆，该转运体主要在小脑中表达。EAAT4编码的转运活性对L-天冬氨酸和L-谷氨酸具有高表观亲和力，并且其药理学特征与先前描述的小脑转运活性一致。在表达EAAT4的非洲爪蟾卵母细胞中，L-天冬氨酸和L-谷氨酸引发了主要由氯离子介导的电流。这种氯离子电导不受阻断内源性卵母细胞氯离子通道的成分的阻断。因此，EAAT4将神经递质的再摄取与增加氯离子通透性的机制结合在一起，这两者均可调节兴奋性神经传递。
