Volatile aromatic Anesthetics variably impact human γ-aminobutyric acid type a receptor function
Volatile aromatic Anesthetics variably impact human γ-aminobutyric acid type a receptor function
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DOI：
10.1213/01.ane.0000282829.21797.97
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发表时间：
2007-11-01
影响因子：
5.7
通讯作者：
Raines, Douglas E.
中科院分区：
文献类型：
--
作者：
Kelly, Elizabeth W.;Solt, Ken;Raines, Douglas E.
γ -氨基丁酸A型（GABA(A)）和n -甲基- d -天冬氨酸（NMDA）受体分别是中枢神经系统中重要的抑制性和兴奋性神经递质受体。在面对有害刺激时产生固定所需的浓度下，挥发性芳香麻醉药不同程度地抑制NMDA受体，强烈表明它们也作用于其他目标以产生固定。在这项研究中，我们试图评估GABAA受体在介导挥发性芳香麻醉剂的行为行为中发挥的潜在作用。方法：采用电生理技术定量测定8种挥发性芳香麻醉药和3种临床麻醉药对爪蟾卵母细胞α (1) β (2) γ (2)_GABA(A)受体介导电流表达的影响。结果：在相同的最低肺泡麻醉浓度倍数下，挥发性芳香麻醉药对低浓度GABA引发的GABAA受体介导电流的增强程度差异很大。一般来说，麻醉药抑制NMDA受体最多，增强GABA受体最少。在临床麻醉药异氟烷、氟烷和环丙烷中，也观察到GABA和NMDA受体的麻醉效力之间的相互关系。对GABA浓度范围的研究表明，挥发性芳香麻醉药通过将打开-关闭（门控）平衡转变为开放通道状态来增强GABAA受体的活性。结论：这些发现表明，GABAA受体对挥发性麻醉剂的行为作用有不同的贡献，并暗示麻醉作用对NMDA和GABA受体的分子决定因素有明显不同。（Anesth Analg 2007;105:1287-92）
The gamma-aminobutyric acid type A (GABA(A)) and N-methyl-D-aspartate (NMDA) receptors are important inhibitory and excitatory neurotransnmitter receptors, respectively, in the central nervous system. At the concentrations required to produce immobility in the face of a noxious stimulus, volatile aromatic anesthetics inhibit NMDA receptors to varying degrees, strongly suggesting that they also act at other targets to produce immobilization. In this study, we sought to assess the potential role that GABAA receptors play in mediating the behavioral actions of volatile aromatic anesthetics. METHODS: Electrophysiological techniques were used to quantify the effects of eight volatile aromatic anesthetics and three clinical anesthetics on currents mediated by alpha(1)beta(2)gamma(2)_GABA(A) receptors expressed in Xenopus oocytes. RESULTS: At equivalent minimal alveolar anesthetic concentration multiples, volatile aromatic anesthetics vary widely in the degrees to which they enhance GABAA receptor-mediated currents elicited by low concentrations of GABA. In general, anesthetics that inhibit NMDA receptors most, enhanced GABA, receptors least. This reciprocal relationship between anesthetic potency on GABA, versus NMDA receptors was also observed for the clinical anesthetics isoflurane, halothane, and cyclopropane. Studies using a range of GABA concentrations indicated that volatile aromatic anesthetics enhance GABAA receptor activity by shifting the open-close (gating) equilibrium towards the open channel state. CONCLUSIONS: These findings suggest that GABAA receptors contribute variably to the behavioral actions of volatile anesthetics and imply that the molecular determinants of anesthetic action on NMDA and GABA, receptors are distinctly different. (Anesth Analg 2007;105:1287-92)