Conti Fiorenzo, Minelli Andrea, Melone Marcello
Dipartimento di Neuroscienze, Sezione di Fisiologia, Università Politecnica delle Marche, Via Tronto 10/A, Torrette di Ancona, I-60020 Ancona, Italy.
Brain Res Brain Res Rev. 2004 Jul;45(3):196-212. doi: 10.1016/j.brainresrev.2004.03.003.
The extracellular levels of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the mammalian cerebral cortex, are regulated by specific high-affinity, Na+/Cl- dependent transporters. Four distinct genes encoding GABA transporters (GATs), named GAT-1, GAT-2, GAT-3, and BGT-1 have been identified using molecular cloning. Of these, GAT-1 and -3 are expressed in the cerebral cortex. Studies of the cortical distribution, cellular localization, ontogeny and relationships of GATs with GABA-releasing elements using a variety of light and electron microscopic immunocytochemical techniques have shown that: (i) a fraction of GATs is strategically placed to mediate GABA uptake at fast inhibitory synapses, terminating GABA's action and shaping inhibitory postsynaptic responses; (ii) another fraction may participate in functions such as the regulation of GABA's diffusion to neighboring synapses and of GABA levels in cerebrospinal fluid; (iii) GATs may play a role in the complex processes regulating cortical maturation; and (iv) GATs may contribute to the dysregulation of neuronal excitability that accompanies at least two major human diseases: epilepsy and ischemia.
γ-氨基丁酸（GABA）是哺乳动物大脑皮层中的主要抑制性神经递质，其细胞外水平由特定的高亲和力、依赖Na⁺/Cl⁻的转运体调节。利用分子克隆技术已鉴定出四个编码GABA转运体（GATs）的不同基因，分别命名为GAT-1、GAT-2、GAT-3和BGT-1。其中，GAT-1和GAT-3在大脑皮层中表达。运用多种光学和电子显微镜免疫细胞化学技术，对GATs在皮层的分布、细胞定位、个体发生以及与GABA释放元件的关系进行研究，结果表明：（i）一部分GATs处于关键位置，可在快速抑制性突触处介导GABA摄取，终止GABA的作用并塑造抑制性突触后反应；（ii）另一部分可能参与诸如调节GABA向邻近突触的扩散以及脑脊液中GABA水平等功能；（iii）GATs可能在调节皮层成熟的复杂过程中发挥作用；（iv）GATs可能导致至少两种主要人类疾病（癫痫和缺血）所伴随的神经元兴奋性失调。
