布格呋喃抗焦虑及抑郁作用的电生理机制  

Electrophysiology mechanisms of 4-butyl-alpha-agarofuran: a new anxiolytic and antidepressant drug

作　　者：陈春林 王伟平 王玲 王晓良 

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2013年第1期38-44,共7页Acta Pharmaceutica Sinica

基　　金：国家“重大新药创制”科技重大专项(2012ZX09301002-004)

摘　　要：研究布格呋喃(AF-5)抗焦虑及抑郁作用的电生理学机制。采用全细胞膜片钳技术,观察AF-5对原代培养大鼠皮层神经元上电压依赖性钠离子通道、电压依赖性钾离子通道、电压依赖性L-型钙离子通道、γ-氨基丁酸(GABA)依赖的氯离子通道以及稳定转染于HEK293细胞系上Kv2.1通道电流的影响。结果表明,AF-5能明显抑制原代培养大鼠皮层神经元上电压依赖性延迟整流钾电流(IK(DR))、L-型钙通道电流(IL-Ca)以及稳定转染于HEK293细胞系上Kv2.1通道电流,其IC50分别为6.17、4.4和5.29μmol.L 1,但对电压依赖性钠通道电流(INa)、瞬时外向钾电流(IK(A))以及GABA介导的氯离子通道电流的抑制作用较弱。研究表明,AF-5的抗焦虑及抑郁作用可能与其抑制以Kv2.1为主的神经元IK(DR)及IL-Ca有关。To investigate the electrophysiology mechanisms of new anxiolytic and antidepressant drug： 4butyl-alpha-agarofuran（AF-5）,patch clamp-recording was used to test the effects of AF-5 on voltage-dependent sodium currents,voltage-dependent potassium currents,L-type voltage-dependent calcium currents and GABA dependent Cl currents in primary cultured rat cortical neurons.Effects of AF-5 on Kv2.1 currents,expressed stably in HEK293 cells,were also tested.Our results showed that,delayed rectifier potassium currents（IK（DR））,L-type voltage-dependent calcium currents（IL-Ca） in primary cultured rat cortical neurons and Kv2.1 currents in HEK293 cells were significantly inhibited by AF-5,with IC50 as 6.17,4.4 and 5.29 μmol.L 1 respectively.However,voltage-dependent sodium currents（INa）,GABA dependent Cl currents and transient outward potassium currents（IK（A）） in primary cultured rat cortical neurons were not significantly blocked by AF-5.Our results concluded that,blocked IK（DR） and IL-Ca currents may be one of the mechanisms of anxiolytic and antidepression actions of AF-5.

关 键 词：布格呋喃 延迟整流钾通道电流 电压依赖性L-型钙通道电流 KV2 1 膜片钳 

分 类 号：R963[医药卫生—微生物与生化药学]