Extrasynaptic GABAA receptors: form, pharmacology, and function.
Extrasynaptic GABAA receptors: form, pharmacology, and function.
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DOI：
10.1523/jneurosci.3340-09.2009
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发表时间：
2009-10-14
期刊：
影响因子：
--
通讯作者：
Cope DW
中科院分区：
文献类型：
--
作者：
Belelli D;Harrison NL;Maguire J;Macdonald RL;Walker MC;Cope DW
GABA是CNS中的主要抑制性神经递质，并通过GABAA和GABAB受体起作用。最近，已经描述了一种新形式的GABAA受体介导的抑制，称为“强直性”抑制。而突触GABAA受体的基础经典的'阶段性' GABAA受体介导的抑制（抑制性突触后电流），'紧张性' GABAA受体介导的抑制的结果从突触外受体的激活低浓度的环境GABA。突触外GABAa受体由传递生物物理性质的受体亚基组成，所述生物物理性质理想地适合于产生持续抑制，并且与其突触对应物在结构和功能上不同。这个小型研讨会的审查强调正在进行的工作，研究重组和天然突触外GABAA受体的特性，以及内源性和临床相关药物的优先靶向。此外，它强调了突触外GABAA受体在整个CNS的GABA能抑制中的重要作用，并将其确定为生理和病理生理过程中的主要参与者。
GABA is the principal inhibitory neurotransmitter in the CNS, and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor mediated inhibition, termed ‘tonic’ inhibition, has been described. Whereas synaptic GABAA receptors underlie classical ‘phasic’ GABAA receptor-mediated inhibition (inhibitory post-synaptic currents), ‘tonic’ GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition, and are pharmacologically and functionally distinct from their synaptic counterparts. This mini-symposium review highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors, and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS, and identifies them as a major player in both physiological and pathophysiological processes.