神经活性甾体通过选择性增强由含δ亚基的GABAA受体介导的紧张性抑制来降低神经元兴奋性。
Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors.
作者信息
Stell Brandon M, Brickley Stephen G, Tang C Y, Farrant Mark, Mody Istvan
机构信息
Department of Neurology, The David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
出版信息
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14439-44. doi: 10.1073/pnas.2435457100. Epub 2003 Nov 17.
Abstract
Neuroactive steroids are potent modulators of gamma-aminobutyric acid type A receptors (GABAARs), and their behavioral effects are generally viewed in terms of altered inhibitory synaptic transmission. Here we report that, at concentrations known to occur in vivo, neuroactive steroids specifically enhance a tonic inhibitory conductance in central neurons that is mediated by extrasynaptic delta subunit-containing GABAARs. The neurosteroid-induced augmentation of this tonic conductance decreases neuronal excitability. Fluctuations in the circulating concentrations of endogenous neuroactive steroids have been implicated in the genesis of premenstrual syndrome, postpartum depression, and other anxiety disorders. Recognition that delta subunit-containing GABAARs responsible for a tonic conductance are a preferential target for neuroactive steroids may lead to novel pharmacological approaches for the treatment of these common conditions.
摘要
神经活性甾体是γ-氨基丁酸A型受体（GABAARs）的强效调节剂，其行为效应通常被认为是通过改变抑制性突触传递来实现的。在此我们报告，在已知的体内存在浓度下，神经活性甾体特异性增强中枢神经元中的一种紧张性抑制电导，该电导由含突触外δ亚基的GABAARs介导。神经甾体诱导的这种紧张性电导增强会降低神经元兴奋性。内源性神经活性甾体循环浓度的波动与经前综合征、产后抑郁症及其他焦虑症的发生有关。认识到负责紧张性电导的含δ亚基的GABAARs是神经活性甾体的优先作用靶点，可能会为治疗这些常见病症带来新的药理学方法。
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