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首页> 外文会议>International Conference on Basic and Systemic Mechanisms of Anesthesia >beta3-containing GABA_A receptors mediate the immobilizing and, in part, the hypnotic actions of etomidate and propofol
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beta3-containing GABA_A receptors mediate the immobilizing and, in part, the hypnotic actions of etomidate and propofol

机译：含有β3的GABA_A受体介导固定，部分地，部分地，依托咪酯和异丙酚的催眠作用

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The molecular mechanisms underlying general anesthesia are only beginning. to be understood. In mis summary, we describe how the role of specific GABA_A receptor subtypes in mediating the clinically relevant actions of general anesthetics has been defined by genetic studies in vivo. In particular, we describe our findings with mice engineered to contain a point mutation, N265M, in the beta3 subunit of the GABA_A receptor. This mutation has previously been shown to render recombinant beta3-containing GABA_A receptors essentially insensitive to etomidate and propofol. beta3(N265M) mice exhibited a completely abolished immobilizing response to etomidate and propofol, as measured by loss of hindlimb withdrawal reflexes. In addition, the respiratory depressant action of etomidate and propofol, as determined by blood gas analysis, was almost absent in beta3(N265M) mice. Furthermore, there was a significantly reduced hypnotic response, as measured by loss of righting reflex duration, compared with wild-type mice, In contrast, sedation, as measured by a decrease in motor activity, and the cardiac depressant and hypothermic effects, as determined by radiotelemetry, remained unchanged in the mutant mice. We conclude that the immobilizing and respiratory depressant and, in part, the hypnotic action of etomidate and propofol, but not the cardiac, hypothermic and sedative effects, are mediated by beta3-containing GABA_A receptor subtypes.
机译：潜在麻醉的分子机制只开始。被理解。在MIS概述中，我们描述了特定GABA_A受体亚型在介导一般麻醉剂的临床相关行动的角色是如何通过体内遗传学研究定义的。特别是，我们用工程化的小鼠描述我们的小鼠在GABA_A受体的β3亚基中含有点突变N265M的小鼠。先前已被证明该突变使含有重组的β3的GABA_A受体基本上对戊胺和异丙酚的不敏感。 β3（N265M）小鼠表现出对戊胺和异丙酚的完全废除的固定反应，如通过后肢戒断反射的丧失测量。此外，通过血气分析确定的替代和异丙酚的呼吸抑制作用作用几乎不存在于β3（N265M）小鼠中。此外，与野生型小鼠相比，通过丧失抗反射持续时间来测量的催眠反应显着降低，相比之下，通过降低电机活性来测量，以及所确定的心脏抑制剂和低温效应来测量通过无线电记录，在突变小鼠中保持不变。我们得出结论，固定化和呼吸抑制剂，部分地，部分地，依托咪啶和异丙酚的催眠作用，但不是心脏，低温和镇静作用，由含β3的GABA_A受体亚型介导。

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