氯胺酮亚单位依赖性地抑制人类神经根烟碱乙酰胆碱受体

The human neuronal nicotinic acetylcholine receptors are inhibited by ketamine with a subunit-dependent manner

目的研究氯胺酮是否通过作用于人类神经根烟碱乙酰胆碱受体而产生全麻作用。方法采用脂质体转染技术在非洲爪蟾卵母细胞上表达由α(α2,α3,α4)和β(β2,β4)亚单位构成的人类神经根烟碱乙酰胆碱受体,利用双极电压钳技术研究氯胺酮对人类神经根烟碱乙酰胆碱受体的作用。结果氯胺酮以非竞争性方式抑制人神经根乙酰胆碱受体。氯胺酮对包含β4亚单位的乙酰胆碱受体更敏感。其对包含β4亚单位的乙酰胆碱受体的IC50是9·5～29μmol/L,而对包含β2亚单位的乙酰胆碱受体的IC50是50～92μmol/L。结论氯胺酮可亚单位依赖性地抑制人类神经根烟碱乙酰胆碱受体,对β亚单位更敏感。

Objective To study whether ketamine producing anesthesia is through its effect on the human neuronal nicotinic acetylcholine receptors （hnAChRs）. Methods Heteromeric human neuronal nAChR （hnAChR channels α2β2, α2β4, α3β2,α3β4, α4β2, α4β4 ） were expressed in Xenopus oocytes,and effects of ketamine were studied using the two-electrode voltage-clamp technique. Result Ketamine inhibited hnAChRs in a noncompetitive manner. The receptors containing β4 subunits were more sensitive to ketamine than those containing β2 subunits. The inhibition concerntration for half- maximal response （IC50） values of ketamine hnAChRs composed of β4 subunits were 9.5-29/μmol/L, whereas those of β2 subunits were 50-92 /μmol/L. Conclusion Human nAChRs are inhibited by ketamine at concentrations possibly achieved during anesthesia in a subunit-dependent manner, with β subunits being more sensitive than a subunit.