GABA(A) Receptor Dynamics and Constructing GABAergic Synapses.
GABA(A) Receptor Dynamics and Constructing GABAergic Synapses.
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DOI：
10.3389/neuro.02.007.2008
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发表时间：
2008
影响因子：
4.8
通讯作者：
Moss SJ
中科院分区：
文献类型：
--
作者：
Tretter V;Moss SJ
GABAA受体位于中枢和外周神经系统中的大多数神经元上，在那里它们介导神经递质γ-氨基丁酸的重要作用。在发育早期，GABA的营养特性允许神经系统的健康发育。大多数神经元在生命早期具有高的细胞内Cl-浓度，这是由于Cl-泵KCC 2的晚期功能表达，因此GABA在这个阶段具有兴奋作用。当KCC 2的高表达和激活时，GABA呈现其抑制作用，而谷氨酸作为主要的兴奋性神经递质起作用。像所有的多亚基膜蛋白的GABAA受体组装在ER中，并通过高尔基体和剩余的分泌途径到细胞表面，在那里它介导GABA的行动，直接在突触或在突触外的网站响应周围的GABA提供一个基础的紧张性抑制状态。为了适应不断变化的需求和信息状态，GABA能系统是高度动态的。这包括亚型特异性运输到细胞中的不同位置，通过与支架分子的相互作用调节流动性，翻译后修饰，其直接影响通道功能或与其他蛋白质的相互作用，最后是表面和细胞内受体池之间的动态交换，其使受体准备再循环到表面或降解。在这里，我们给出了一个概述GABAA受体的功能和分子动力学，在维持兴奋和抑制之间的平衡，并在网络活动的变化发挥了重要作用的当前理解。
GABAA receptors are located on the majority of neurons in the central and peripheral nervous system, where they mediate important actions of the neurotransmitter gamma-aminobutyric acid. Early in development the trophic properties of GABA allow a healthy development of the nervous system. Most neurons have a high intracellular Cl-concentration early in life due to the late functional expression of the Cl-pump KCC2, therefore GABA has excitatory effects at this stage. Upon higher expression and activation of KCC2 GABA takes on its inhibitory effects while glutamate functions as the major excitatory neurotransmitter. Like all multisubunit membrane proteins the GABAA receptor is assembled in the ER and travels through the Golgi and remaining secretory pathway to the cell surface, where it mediates GABA actions either directly at the synapses or at extrasynaptic sites responding to ambient GABA to provide a basal tonic inhibitory state. In order to adapt to changing needs and information states, the GABAergic system is highly dynamic. That includes subtype specific trafficking to different locations in the cell, regulation of mobility by interaction with scaffold molecules, posttranslational modifications, that either directly affect channel function or the interaction with other proteins and finally the dynamic exchange between surface and intracellular receptor pools, that either prepare receptors for recycling to the surface or degradation. Here we give an overview of the current understanding of GABAA receptor functional and molecular dynamics that play a major part in maintaining the balance between excitation and inhibition and in changes in network activity.
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