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Effects of general anesthetics on molecular dynamics and conformation of neuronal receptor channel protains - Molecular mechanism of general anesthesia -

全身麻醉药对神经元受体通道蛋白分子动力学和构象的影响 - 全身麻醉的分子机制 -

基本信息

批准号：
13470319
负责人：
MASHIMO Takashi
金额：
$ 10.37万
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：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

1)Effects of inhalational anesthetics on recombinant GABA_A receptors and NMDA receptors expressed in Xenopus oocyte : Different combinations of GABA_A receptor subunits (α1β2 and α1β2γ2s) and NMDA receptor (ζ1ε1) were injected to Xenopus oocyte followed by incubation at 20℃ for >48h. The electrophystological recordings were made by using the two electrode-voltage champ technique. Volatile anesthetics potentiated GABA-induced current in dose dependent manners in the α1β2 and α1β2γ2s receptors, but xenon (Xe), nitrous oxide (N_2O) showed no significant potentiation. On the contrary, volatile anesthetics did not affect NMDA-induced current in the ζ1ε1 receptor, Xe and N_2O depressed it dose-dependently.2)Effects of Xe and N_2O on the human neuronal (α_7)_5 nAch receptor expressed in Xenopus oocyte : At clinically relevant concentrations, Xe and N_2O reversibly inhibited the ACh-induced currents of the (α_7)_5 nAch receptor in a concentration-dependent manner. The inhibitory actions of both anesthetics at the (α_7)_5 nAch were non-competitive and voltage-independent.3)Effects of inhalational anesthetics on human-cloned 5-HT_3 receptor expressed in Xenopus oocyte : Inhalational anesthetics produced deverse effects on the 5-HT_3 receptor. Both halothane and isoflurane enhanced 5-HT_3 receptor function in a concentration-dependent manner. Sevoflurane inhibited the 5-HT-induced current noncopmetitively, whereas Xe and N_2O inhibited the 5-HT_3 receptor competitively. The results suggest that inhalational anesthetics acts on neuronal receptors in the specific manner.

1)吸入麻醉剂对爪蟾卵母细胞表达重组GABA_A受体和NMDA受体的影响：将GABA_A受体亚基（α1β2和α1β2γ2s）和NMDA受体（α 1ε1）的不同组合注射到爪蟾卵母细胞中，然后在20℃孵育> 48 h。采用双电极电压钳技术记录肌电。在α1β2和α1β2γ2s受体上，挥发性麻醉药呈剂量依赖性地增强GABA诱发的电流，而氙（Xe）、一氧化二氮（N_2O）则无明显增强作用。（2）N_2O和N_2O对非洲爪蟾卵母细胞表达的人神经元（α_7）_5nAch受体的影响：在临床相关浓度下，N_2O和N_2O以浓度依赖的方式可逆地抑制（α_7）_5nAch受体的乙酰胆碱诱导电流。3）吸入麻醉药对爪蟾卵母细胞5-HT_3受体表达的影响：吸入麻醉药对爪蟾卵母细胞5-HT_3受体表达有相反的作用。氟烷和异氟醚均呈浓度依赖性地增强5-HT_3受体功能。七氟醚非竞争性地抑制5-HT诱导的电流，而N_2O和N_2O竞争性地抑制5-HT_3受体。结果提示，吸入麻醉药对神经元受体的作用具有特异性。