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）吸入麻醉药对异武卵母细胞中表达的重组GABA_A受体和NMDA受体的影响：GABA_A受体亚基（α1β2和α1β2γ2S）和NMDA受体（NMDA受体）和NMDA受体（ζ1ε1）的不同组合被注入了Xenopus to Xenopus ocyte -exenep foref forepy forepy forepy forepy forsepoy formocy formocy formocy。通过使用两种电极电压冠军技术进行电生理记录。挥发性麻醉药在α1β2和α1β2γ2S受体中以剂量依赖性方式引起了GABA诱导的电流，但是XENON（XE），一氧化二氮（N_2O）没有明显的潜力。与鲜明的相反，挥发性麻醉剂不会影响ζ1ε1受体，Xe和N_2O中NMDA诱导的电流的抑制作用。（α_7）_5 NACH受体的ACh诱导电流以浓度依赖性方式。两种麻醉药在（α_7）_5 NACH上的抑制作用都是非竞争性和无效的独立的。硫烷和异氟烷都以浓度依赖性方式增强了5-HT_3受体功能。 Sevoflurane抑制了5-HT诱导的当前非电容性，而XE和N_2O竞争抑制了5-HT_3受体。结果表明，异常麻醉剂以特定方式作用于神经元受体。