β2-nAChR促进小鼠海马CA1和CA3锥体神经元GABA_A受体的功能成熟  

β2-nicotinic acetylcholine receptor promotes development of GABA_A receptors in mouse hippocampal CA1 and CA3 pyramidal neurons

作　　者：郑超[1] 黄艳 张环环[1] 查盈盈[1] 汪萌芽[1] ZHENG Chao;HUANG Yan;ZHANG Huanhuan;ZHA Yingying(WANG Mengya Cell Electrophysiology Laboratory,Wannan Medical College,Wuhu 241002,China)

机构地区：[1]皖南医学院细胞电生理研究室,安徽芜湖241002

出　　处：《南方医科大学学报》2018年第9期1045-1051,共7页Journal of Southern Medical University

基　　金：国家自然科学基金(31200828;31271155;81601158);安徽省高校优秀青年人才支持计划重点项目(gxyq ZD2016175);安徽高校自然科学研究项目(KJ2018A0266);皖南医学院博士科研启动基金项目(rcqd201609)~~

摘　　要：目的探讨β2-烟碱型乙酰胆碱受体(β2-n ACh R)在海马CA1和CA3锥体神经元的A型γ-氨基丁酸受体(GABA_A-R)发育中的作用。方法应用β2-n ACh R基因敲除小鼠(β2-KO组)制备急性分离的海马CA1和CA3锥体神经元,应用穿孔膜片钳记录技术记录GABA_A-R选择性激动剂蝇蕈醇在CA1和CA3锥体神经元诱导的GABA电流,测试其平衡电位(E_(Mus))和动力学指标,并与野生型小鼠(WT组)进行比较。结果β2-KO组小鼠(n=4)CA1锥体神经元(n=7)的E_(Mus)为-31.7±3.5 m V,与WT组相比向去极化偏移(P<0.05);CA3锥体神经元(n=4)的E_(Mus)为-16.1±4.6 m V,同样较WT组偏向去极化方向(P<0.01);与WT组小鼠不同,β2-KO组小鼠CA3和CA1神经元的E_(Mus)差异有统计学意义(P<0.05)。β2-KO组小鼠CA1和CA3神经元上都显示GABA_A-R的失敏显著减慢,衰减时间分别为2.2±0.2 s、3.2±0.1 s(WT组为1.6±0.1 s、2.3±0.1 s,P<0.05或P<0.01)。结论含β2的n ACh R可能参与促进小鼠海马CA1和CA3锥体细胞中GABA_A-R的功能成熟。Objective To explore the role of β2-nicotinic acetylcholine receptor（β2-n ACh R） in the development of γ-aminobutyric acid A type receptors（GABA_A-Rs） in hippocampal CA1 and CA3 pyramidal neurons of mice. Methods The hippocampal CA1 and CA3 pyramidal neurons were acutely isolated from β2-n ACh R gene knockout（β2-KO group） mice.GABA currents in CA1 and CA3 pyramidal neurons were induced with the selective GABA_A-R agonist muscimol and recorded using perforated patch-clamp recording technique. The GABA currents of CA1 and CA3 pyramidal neurons were tested for their equilibrium potentials（E_（Mus）s） and kinetic parameters and were compared with the measurements in wild-type mice（WT group）. Results The mean E_（Mus） of CA1 neurons（n=7） of β2-KO mice（n=4） was-31.7±3.5 m V, showing an obvious depolarizing shift compared with the WT mice（P0.05）; the mean E_（Mus）of CA3 neurons（n=4） was-16.1±4.6 m V, also showing a depolarizing shift（P0.01）. The difference in the E_（Mus）s between CA3 and CA1 neurons in β2-KO mice, but not in WT mice, was significant（P0.05）. The GABA_A-R desensitization was significantly slowed down in both CA1 and CA3 neurons of β2-KO mice, with decay time of 2.2±0.2 s and 3.2±0.1 s, respectively, significantly longer than those in WT mice（1.6±0.1 s and 2.3±0.1 s, respectively; P0.05）. Conclusion β2-containing n ACh Rs may promote the functional maturation of GABA_A-R in CA1 and CA3 pyramidal cells in mouse hippocampus.

关 键 词：海马 β2-烟碱型乙酰胆碱受体 基因敲除 A型γ-氨基丁酸受体 蝇蕈醇诱导电流的平衡电位 动力学指标 

分 类 号：R338[医药卫生—人体生理学]