Ghrelin抑制A型钾通道电流对小鼠黑质多巴胺能神经元兴奋性的影响  

GHRELIN ENHANCES THE EXCITABILITY OF SUBSTANTIA NIGRA DOPAMINERGIC NEURONS IN MICE VIA INHIBITION OF A-TYPE POTASSIUM CHANNELS

作　　者：薛宝 常晓丽 贾璐 石丽敏 谢俊霞 XUE Bao;CHANG Xiaoli;JIA Lu;SHI Limin;XIE Junxia(Department of Physiology, Qingdao University Medical College, Qingdao 266071, China)

机构地区：[1]青岛大学医学部基础医学院生理学教研室,山东青岛266071

出　　处：《青岛大学学报（医学版）》2018年第2期127-129,133,共4页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金项目(81430024;31671054);中国博士后科学基金第61批面上项目(2017M610412);青岛市源头创新计划(应用研究专项-青年专项)

摘　　要：目的探讨ghrelin是否通过抑制A型钾通道电流增强正常小鼠黑质多巴胺能神经元的自发放电。方法应用出生15~20d的C57BL/6小鼠制备脑片,脑片全细胞膜片钳技术观察ghrelin对黑质多巴胺能神经元自发放电频率及A型钾通道电流幅度的影响。结果小鼠黑质脑片灌流100nmol/L ghrelin,多巴胺能神经元自发放电频率明显升高(n=5,t=3.55,P<0.05);应用A型钾通道阻断剂4-AP可以完全阻断ghrelin的细胞兴奋效应。应用100nmol/L ghrelin可以明显抑制A型钾电流的电流幅度(n=5,t=5.67,P<0.01)。结论 Ghrelin能够提高正常小鼠黑质多巴胺能神经元的兴奋性,其机制可能是通过抑制A型钾通道电流实现的。Objective To investigate whether ghrelin enhances the spontaneous discharge of substantia nigra dopaminergic neurons in normal mice via inhibition of A-type potassium channel current（IA）. Methods Brain slices of the substantia nigra were prepared from C57BL/6 mice（aged 15-20 d）.The effects of ghrelin on the spontaneous discharge frequency of substantia nigra dopaminergic neurons and IA amplitude were observed by whole-cell patch clamp technique. Results The spontaneous discharge frequency of dopaminergic neurons was significantly increased after application of 100 nmol/L ghrelin to the brain slices of the substantia nigra（n=5,t=3.55,P〈0.05）.4-AP（A-type potassium channel blocker）can block ghrelin-enhanced excitability of dopaminergic neurons completely.100 nmol/L ghrelin significantly inhibited the amplitude of IA（n=5,t=5.67,P〈0.01）. Conclusion Ghrelin can improve the excitability of dopaminergic neurons in the substantia nigra in normal mice,possibly by inhibiting IA.

关 键 词：胃促生长素 黑质 多巴胺能神经元 A型钾通道 

分 类 号：R338.8[医药卫生—人体生理学]