Muscimol is a psychoactive isoxazole derived from the mushroom Amanita muscaria and a potent orthosteric agonist of the GABA_A receptor. The binding of [³H]muscimol has been used to evaluate the distribution of GABA_A receptors in the brain, and studies of modulation of [³H]muscimol binding by allosteric GABAergic modulators such as barbiturates and steroid anesthetics have provided insight into the modes of action of these drugs on the GABA_A receptor. It has, however, not been feasible to directly apply interaction parameters derived from functional studies to describe the binding of muscimol to the receptor. Here, we employed the Monod-Wyman-Changeux concerted transition model to analyze muscimol binding isotherms. We show that the binding isotherms from recombinant α1β3 GABA_A receptors can be qualitatively predicted using electrophysiological data pertaining to properties of receptor activation and desensitization in the presence of muscimol. The model predicts enhancement of [³H]muscimol binding in the presence of the steroids allopregnanolone and pregnenolone sulfate, although the steroids interact with distinct sites and either enhance (allopregnanolone) or reduce (pregnenolone sulfate) receptor function. We infer that the concerted transition model can be used to link radioligand binding and electrophysiological data.

中文翻译：

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GABAA受体的变构调节剂增强Muscimol结合和门控：占用与状态功能。

Muscimol是一种精神活性异恶唑，衍生自蘑菇鹅膏菌（Amanita muscaria），并且是GABA _A受体的强效正构激动剂。[ ³ H] muscimol的结合已用于评估脑中GABA _A受体的分布，而变构GABA能量调节剂（如巴比妥酸盐和类固醇麻醉剂）对[ ³ H] muscimol结合的调节作用的研究为这种模式提供了见解这些药物对GABA _A的作用受体。然而，直接应用源自功能研究的相互作用参数来描述麝香酚与受体的结合尚不可行。在这里，我们采用了Monod-Wyman-Changeux协调转换模型来分析muscimol结合等温线。我们表明，从重组的结合等温线α 1个β 3 GABA_甲受体可以定性使用关于在蝇蕈醇的存在下受体活化和脱敏的性质的电生理数据预测。该模型预测[ ³尽管类固醇与不同的部位相互作用并增强（allopregnanolone）或降低（硫酸孕烯醇酮）受体的作用，但在类固醇allopregnanolone和硫酸孕烯醇酮存在下H] muscimol结合。我们推断，协调的过渡模型可用于链接放射性配体结合和电生理数据。