Violet J M, Downie D L, Nakisa R C, Lieb W R, Franks N P
Biophysics Section, Blackett Laboratory, Imperial College of Science, Technology, and Medicine, London, United Kingdom.
Anesthesiology. 1997 Apr;86(4):866-74. doi: 10.1097/00000542-199704000-00017.
Nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of fast neurotransmitter-gated receptor channels that includes the gamma-aminobutyric acidA (GABAA), glycine and serotonin type 3 (5-HT3) receptors. Most previous work on the interactions of general anesthetics with nAChRs has involved the muscle-type receptor. The authors investigate the effects of general anesthetics on defined mammalian neuronal and muscle nAChRs expressed in Xenopus oocytes.
Complementary deoxyribonucleic acid (cDNA) or messenger ribonucleic acid (mRNA) encoding for various neuronal or muscle nAChR subunits was injected into Xenopus oocytes, and the resulting ACh-activated currents were studied using the two-electrode voltage-clamp technique. The effects of halothane, isoflurane, sevoflurane, and propofol on the peak acetylcholine-induced currents were investigated, and concentration-response curves were constructed.
The neuronal nAChRs were found to be much more sensitive to general anesthetics than were the muscle nAChRs, with IC50 concentrations being 10- to 35-fold less for the neuronal receptors. For the inhalational general anesthetics, the IC50 concentrations were considerably less than the free aqueous concentrations that cause general anesthesia in mammals. In addition, qualitative (dependence on acetylcholine concentration) and quantitative (steepness of concentration-response curves) differences in the anesthetic interactions between the neuronal and muscle nAChRs suggest that different mechanisms of inhibition may be involved.
Although there is considerable uncertainty about the physiologic roles that neuronal nAChRs play in the central nervous system, their extraordinary sensitivity to general anesthetics, particularly the inhalational agents, suggests they may mediate some of the effects of general anesthetics at surgical, or even subanesthetic, concentrations.
烟碱型乙酰胆碱受体（nAChRs）是快速神经递质门控受体通道超家族的成员，该超家族还包括γ-氨基丁酸A（GABAA）受体、甘氨酸受体和5-羟色胺3型（5-HT3）受体。此前关于全身麻醉药与nAChRs相互作用的大多数研究都涉及肌肉型受体。作者研究了全身麻醉药对非洲爪蟾卵母细胞中表达的特定哺乳动物神经元和肌肉nAChRs的影响。
将编码各种神经元或肌肉nAChR亚基的互补脱氧核糖核酸（cDNA）或信使核糖核酸（mRNA）注入非洲爪蟾卵母细胞，然后使用双电极电压钳技术研究由此产生的乙酰胆碱激活电流。研究了氟烷、异氟烷、七氟烷和丙泊酚对乙酰胆碱诱导的峰值电流的影响，并构建了浓度-反应曲线。
发现神经元nAChRs对全身麻醉药的敏感性远高于肌肉nAChRs，神经元受体的半数抑制浓度（IC50）低10至35倍。对于吸入性全身麻醉药，IC50浓度远低于在哺乳动物中引起全身麻醉的游离水浓度。此外，神经元和肌肉nAChRs之间麻醉相互作用的定性（对乙酰胆碱浓度的依赖性）和定量（浓度-反应曲线的斜率）差异表明可能涉及不同的抑制机制。
尽管神经元nAChRs在中枢神经系统中所起的生理作用存在很大不确定性，但它们对全身麻醉药，尤其是吸入性麻醉药的非凡敏感性表明，它们可能在手术浓度甚至亚麻醉浓度下介导全身麻醉药的某些作用。
