The dynamic modulation of GABA(A) receptor trafficking and its role in regulating the plasticity of inhibitory synapses.

The dynamic modulation of GABA(A) receptor trafficking and its role in regulating the plasticity of inhibitory synapses.
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DOI:
10.1152/physrev.00015.2010
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发表时间:
2011-07
影响因子:
33.6
通讯作者:
Moss SJ
Moss SJ
中科院分区:
医学1区
文献类型:
--
作者:
Vithlani M;Terunuma M;Moss SJ

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γ-氨基丁酸A型受体(GABAAR)介导大部分快速突触抑制,是抗焦虑、镇静、催眠和抗惊厥药物(包括苯二氮卓类、巴比妥类、神经类固醇和一些全身麻醉药)的主要作用部位。GABAAR是异五聚体配体门控离子通道,发现其集中在抑制性突触后位点,在那里它们介导相位抑制。介导紧张性抑制的突触外GABAAR的专门群体也由神经元表达。阶段性抑制的功效以及因此神经元兴奋性严重依赖于抑制性突触处特定GABAAR亚型的积累。在这里,我们评估神经元如何控制神经元质膜上的GABAARs的数量,以及它们在突触部位的选择性稳定。然后,我们继续研究这些过程对突触抑制强度的影响,以及它们对行为和神经精神疾病病因的可能影响。
γ-aminobutyric acid type-A receptors (GABAARs) mediate the majority of fast synaptic inhibition and are the principle sites of action for anxiolytic, sedative, hypnotic and anti-convulsant agents that include benzodiazepines, barbiturates, neurosteroids and some general anesthetics. GABAARs are hetero-pentameric ligand-gated ion channels that are found concentrated at inhibitory postsynaptic sites where they mediate phasic inhibition. Specialized populations of extrasynaptic GABAARs that mediate tonic inhibition are also expressed by neurons. The efficacy of phasic inhibition and thus neuronal excitability is critically dependent on the accumulation of specific GABAAR subtypes at inhibitory synapses. Here we evaluate how neurons control the number of GABAARs on the neuronal plasma membrane together with their selective stabilization at synaptic sites. We then go on to examine the impact that these processes have on the strength of synaptic inhibition and their possible impact on behavior and the etiology of neuropsychiatric disorders.
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