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Molecular mechanism of anesthesia of xenon : specific or nonspecific effect?

氙气麻醉的分子机制：特异性还是非特异性作用？

基本信息

批准号：
10470317
负责人：
MASHIMO Takashi
金额：
$ 7.94万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470317/
关键词：
anesthetic action mechanism specific non specific xenon nitrous oxide GABA_A recptor NMDA receptor キセノンイソフルランセボフルラン揮発性麻酔薬重水イソフルレン MAC

项目摘要

1) Binding of volatile anesthetics to purple membranes studied by X-ray diffraction.The concentrated purple membranes suspension was sealed in a 1 mm diameter glass capillary which also included buffer solution with or without volatile anesthetic, diiodomethane at its both sides. The X-ray diffraction pattern was recorded on a imaging plate and read by an image scanner. The X-ray diffraction study showed that anesthetics bound specifically to the protein-lipid interfacial region within a trimer near the surface of bacteriorhodopsin in the purple membrane.2) Effects of xenon, nitrous oxide and volatile anesthetics on recombinant GABA_A receptors and recombinant NMDA receptors expressing in Xenopusoocyte.Mouse cDNAs encoding for α1, β2 and γ2s GABA_A receptor subunits, and for ζ1, ε1 NMDA receptor were subcloned into transcription vector. A vector containing each subunit was linearized by an appropriate restriction enzyme to create the template cDNA and cRNA was synthesized in vitro. Different combinations of GABA_A receptor subunits (α1 β2 and α1 β2 γ2s ) and NMDA receptor (ζ1 ε1) were injected to Xenopusoocyte followed by incubation at 20℃ for >48h. The electrophysiological recordings were made by using the two electrode-voltage clamp technique. Volatile anesthetics potentiated GABA-induced current in dose dependent manners in the α1 β2 and α1 β2 γ2s receptors, but xenon and nitrous oxide showed no significant potentiation. On the contrary, volatile anesthetics did not affect NMDA-induced current in the ζ1 ε1 recentor, but xenon and nitrous oxide depressed it dose-dependently.The results suggest that an inert gas, xenon acts on neuronal receptors in the specific manner.

1)用X-射线衍射法研究了挥发性麻醉药与紫膜的结合，将紫膜浓缩液密封在直径为1 mm的玻璃毛细管中，毛细管两侧还包括含有或不含挥发性麻醉药和二碘甲烷的缓冲溶液。将X射线衍射图案记录在成像板上并通过图像扫描仪读取。氙、氧化亚氮和挥发性麻醉剂对异种卵母细胞GABA_A受体和NMDA受体表达的影响：用小鼠cDNA克隆了α1、β2和γ 2sGABA_A受体亚基，以及γ 1、γ 2、γ 3和γ 4 sGABA_A受体亚基，将ε1 NMDA受体亚克隆到转录载体中。通过适当的限制性内切酶将含有每个亚基的载体线性化以产生模板cDNA，并在体外合成cRNA。将GABA_A受体亚单位（α1 β2和α1 β2 γ2s）和NMDA受体（α 1 ε1）的不同组合注入异种卵母细胞，然后在20℃孵育> 48 h。采用双电极电压钳技术进行电生理记录。挥发性麻醉剂以剂量依赖性方式增强α1 β2和α1 β2 γ2s受体中GABA诱导的电流，但氙和一氧化二氮未显示出显著增强作用。相反，挥发性麻醉药对NMDA诱发的电流无影响，而氙和氧化亚氮则呈剂量依赖性地抑制NMDA诱发的电流，提示氙是一种惰性气体，能特异地作用于神经元受体。