Are Extrasynaptic GABAA Receptors Important Targets for Sedative/Hypnotic Drugs?
Are Extrasynaptic GABAA Receptors Important Targets for Sedative/Hypnotic Drugs?
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DOI：
10.1523/jneurosci.5406-11.2012
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发表时间：
2012-03-14
影响因子：
5.3
通讯作者：
Brickley, Stephen G.
中科院分区：
文献类型：
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作者：
Houston, Catriona M.;McGee, Thomas P.;Brickley, Stephen G.
高亲和力的突触外GABA(A)受体被存在于细胞外空间的低环境GABA水平持续激活。由此产生的紧张性电导产生一种形式的分流抑制，能够改变细胞和网络的行为。已有研究表明，神经类固醇、抗癫痫药物和镇静/催眠药物可增强这种紧张性抑制作用。然而，我们表明，镇静/催眠药物增强小鼠小脑紧张性抑制的能力将严重依赖于环境中的GABA水平。例如，我们发现静脉麻醉剂异丙酚只有在周围的GABA水平达到
High-affinity extrasynaptic GABA(A) receptors are persistently activated by the low ambient GABA levels that are known to be present in extracellular space. The resulting tonic conductance generates a form of shunting inhibition that is capable of altering cellular and network behavior. It has been suggested that this tonic inhibition will be enhanced by neurosteroids, antiepileptics, and sedative/hypnotic drugs. However, we show that the ability of sedative/hypnotic drugs to enhance tonic inhibition in the mouse cerebellum will critically depend on ambient GABA levels. For example, we show that the intravenous anesthetic propofol enhances tonic inhibition only when ambient GABA levels are