Kittler Josef T, McAinsh Kristina, Moss Stephen J
Department of Pharmacology, University College London, United Kingdom.
Mol Neurobiol. 2002 Oct-Dec;26(2-3):251-68. doi: 10.1385/MN:26:2-3:251.
Fast synaptic inhibition in the brain is largely mediated by ionotropic GABA receptors, which can be subdivided into GABAA and GABAC receptors based on pharmacological and molecular criteria. GABAA receptors are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are implicated in several diseases including epilepsy, anxiety, depression, and substance abuse. In addition, modulating the efficacy of GABAergic neurotransmission may play a key role in neuronal plasticity. Recent studies have begun to reveal that the accumulation of ionotropic GABAA receptors at synapses is a highly regulated process that is facilitated by receptor-associated proteins and other cell-signaling molecules. This review focuses on recent experimental evidence detailing the mechanisms that control the assembly and transport of functional ionotropic GABAA receptors to cell surface sites, in addition to their stability at synaptic sites. These regulatory processes will be discussed within the context of the dynamic modulation of synaptic inhibition in the central nervous system (CNS).
大脑中的快速突触抑制主要由离子型GABA受体介导，根据药理学和分子标准，该受体可细分为GABAA和GABAC受体。GABAA受体是一系列镇静、抗焦虑和催眠药物的重要治疗靶点，并且与包括癫痫、焦虑、抑郁和药物滥用在内的多种疾病有关。此外，调节GABA能神经传递的效能可能在神经元可塑性中起关键作用。最近的研究开始揭示，离子型GABAA受体在突触处的积累是一个高度受调控的过程，该过程由受体相关蛋白和其他细胞信号分子促进。本综述重点关注最近的实验证据，这些证据详细说明了控制功能性离子型GABAA受体组装和转运到细胞表面位点的机制，以及它们在突触位点的稳定性。这些调节过程将在中枢神经系统（CNS）突触抑制的动态调节背景下进行讨论。
