Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: the effects on agonist enhancement, direct activation, and inhibition.
Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: the effects on agonist enhancement, direct activation, and inhibition.
复制标题
非卤烷麻醉剂对 GABA(A) 受体功能的调节：对激动剂增强、直接激活和抑制的影响。
DOI：
10.1097/00000539-200301000-00024
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发表时间：
2003
影响因子：
5.7
通讯作者：
Forman,StuartA
中科院分区：
文献类型：
--
作者：
Raines,DouglasE;Claycomb,RobertJ;Forman,StuartA
At clinically relevant concentrations, ethers, alcohols, and halogenated alkanes enhance agonist action on the γ-aminobutyric acid A (GABA A) receptor, whereas nonhalogenated alkanes do not. Many anesthetics also directly activate and/or inhibit GABA A receptors, actions that may produce important behavioral effects; although, the effects of nonhalogenated alkane anesthetics on GABA A receptor direct activation and inhibition have not been studied. In this study, we assessed the abilities of two representative nonhalogenated alkanes, cyclopropane and butane, to enhance agonist action, directly activate, and inhibit currents mediated by expressed α 1 β 2 γ 2L GABA A receptors using electrophysiological techniques. Our studies reveal that cyclopro-pane and butane enhance agonist action on the GABA A receptor at concentrations that exceed those required to produce anesthesia. Neither nonhalogenated alkane directly activated nor inhibited GABA A receptors, even at concentrations that approach their aqueous saturated solubilities. These results strongly suggest that the behavioral actions of nonhalogenated alkane anesthetics do not result from their abilities to enhance agonist actions, directly activate, or inhibit α 1 β 2 γ 2L GABA A receptors and are consistent with the hypothesis that electrostatic interactions between anesthetics and their protein binding sites modulate GABA A receptor potency.
