神经元N受体α4β2、α4β4和α7亚型在激动剂作用下功能失敏的特征  

Desensitization characteristics of neuronal α_4β_2、 α_4β_4 and α_7-nicotinic acetylcholine receptors stimulated by their agonist

作　　者：罗王倩[1] 崔文玉[1] 汪海[1,2] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]卫生学环境医学研究所,天津300050

出　　处：《中国药理学通报》2009年第3期406-411,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30371641)

摘　　要：目的探讨激动剂持续或反复作用下SH-EP1细胞株转染表达的神经元α4β2、α4β4和α7亚型N受体功能失敏的特征。方法细胞传代培养3d后以烟碱(α4β2和α4β4)或胆碱(α7)为激动剂,通过喷射给药,采用膜片钳全细胞记录技术研究3种受体亚型功能失敏的药理学特征。结果在分别表达α4β2、α4β4和α7的SH-EP1细胞上喷射给予相应激动剂能够诱发浓度依赖性的内向电流。持续给予激动剂,α7迅速失敏,速度最快,程度最深;α4β4失敏最慢,程度最浅;而α4β2呈先快后慢的双相失敏,失敏速度与程度均居中。反复多次给予激动剂,α4β2失敏最快,而α4β4与α7无明显失敏。结论神经元N受体α4β2、α4β4和α7亚型在激动剂持续或反复作用下功能失敏过程各不相同,这可能与它们在有机磷毒物中毒时过度蓄积的乙酰胆碱持续作用、烟草成瘾时烟碱反复作用所介导的不同效应有关。Aim To investigate the desensitization characteristics of neuronal α4β2、α4β4 and α7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 cell line stimulated by prolonged of repetitive application of agonist. Methods The Whole cell recording configuration of patch-clamp technique was used to study the desensitization characteristics of α4β2、α4β4 and α7-nAChRs in cultured SH-EP1 cells three days after passage by rapid application of nicotine onto the soma of the ceXls. Results Inward currents were elicited by rapid application of agonist in all the three types of SH-EP1 cells in a concentration-dependent manner, α7-nAChRs desensitized the fastest and deepest in the three while α4β4-nAChRs the slowest and lightest under nAChRs desensitized prolonged stimulation, α4β2- the fastest in the three under repetitive stimulation while α4β4 and α7-nAChRs didn＇t have obvious desensitization. Conclusion When stimulated by prolonged of repetitive application of agonist, neuronal α4β2、α4β4 and α7-nicotinic acetylcholine receptors had different desensitization characteristics, which is possibly associated with their roles in organophosphate poisoning inducing persistent stimulation of excessive accumulation of endogenous ACh and in nicotine addiction inducing repetitive stimulation of nicotine.

关 键 词：N受体 有机磷中毒 成瘾 SH—EP1细胞株 膜片钳 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R392.11[医药卫生—基础医学]