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

1)吸入麻醉剂对非洲爪哇卵母细胞表达重组GABA_A受体和N-甲基-D-天冬氨酸受体的影响：将不同组合的α_A受体亚单位(β_2和α_1β_2γ_2s)和N-甲基-D-天冬氨酸受体(ζ_1ε1)注射到非洲爪哇卵母细胞中，20℃孵育48h。电生理记录采用双电极-电压CHAMP技术。挥发性麻醉剂可剂量依赖性地增强α-1-β-2和α-1-β-2-γ-2s受体的电流，而氙气(Xe)和一氧化二氮(N_2O)无明显增强作用。相反，挥发性麻醉药不影响ζ-1-ε-1受体的诱发电流，Xe和N_2O呈剂量依赖性抑制。2)Xe和N_2O对非洲爪哇卵母细胞表达的神经元型(α_7)_5-NACH受体的影响：在临床相关浓度下，Xe和N_2O以浓度依赖的方式可逆地抑制(α_7)_5-NACH受体的ACh诱导电流。两种麻醉药对(α_7)_5 NACH的抑制作用都是非竞争性的，且不依赖于电压。3)吸入麻醉剂对非洲爪哇卵母细胞表达的5-HT3受体的影响：吸入麻醉剂对5-HT3受体有反向作用。氟烷和异氟烷均以浓度依赖的方式增强5-HT3受体的功能。七氟醚非协同抑制5-羟色胺诱发的电流，Xe和N_2O竞争性抑制5-HT3受体。结果提示，吸入麻醉药以特定的方式作用于神经元受体。

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.