【作者】 黄擎；

【导师】 王元银； 王烈成；

【作者基本信息】 安徽医科大学 ， 口腔临床医学， 2008， 硕士

【摘要】 目的运用全细胞膜片钳方法,观察新型精神兴奋剂莫达非尼对培养的海马锥体神经元上GABA受体介导电流的影响,以及KATP通道的开放和关闭在莫达非尼对GABA受体介导电流的调控机制中的影响。本实验通过研究莫达非尼,GABA,以及KATP通道三者之间的关系,从而去探讨莫达非尼在治疗癫痫和镇痛方面可能的作用机制。方法在培养的海马锥体神经元上,进行全细胞膜片钳记录。对照组是单独给与GABA引起的明显脱敏的内向电流(IGABA),实验组分为A组预给药莫达非尼3min后给与GABA引起的内向电流(IGABA),B组预先用格列本脲孵育海马神经元30min后再重复A组给药模式引起的内向电流(IGABA)。结果在培养的海马锥体神经元上,GABA引起电流能被GABAA受体的竞争性阻断剂荷包牡丹碱阻断。单独给予莫达非尼时,明显地抑制了内向电流IGABA,而且莫达非尼在1mM以下时呈浓度依赖性的抑制作用。而格列本脲预处理海马神经元30min后,再单独给予莫达非尼,发现莫达非尼对于IGABA的抑制作用被逆转。结论新型促醒药莫达非尼用于治疗发作性睡眠引起的过度睡眠,不同于传统的兴奋剂,莫达非尼对GABA受体介导电流的调控机制是间接的,莫达非尼对于神经元的保护作用可能与ATP敏感性钾离子通道的开放有关。更多还原

【Abstract】 Objective To study the effects of modafinil, a novel psychoactive drug, on the GABAA receptor-induced current in rat hippocampus pyramidal neurons with whole-cell patch- clamp recordings. The relationship among modafinil, IGABA and KATP channels were tested in order to discover the mechanism of curing epilepsy and analgesia underlying modafinil activity.Methods Whole-cell patch-clamp recordings were applied in cultured hippocampus pyramidal neurons. The control group was applicated GABA (0.1 mM) evoking an inward current (IGABA). The experimental groups were included two groups. In A group: modafinil was pre-perfused the neuron for 3 min in the external solution, then GABA (0.1 mM) was applied for 30 sec. In B group: after the neurons were cultured in the external solution with glibenclamide for 30 min, the protocol of the group A was repeated.Results In cultured hippocampus pyramidal neurons, the GABA-activated currents were blocked by bicuculline, a competitive antagonist of GABAA receptor. After pre- perfusion with modafinil (0.01, 0.1 and 1mM) for 3 min, IGABA was partly blocked in a dose-dependent manner. Pre-treating hippocampus neurons with glibenclamide for 30 min, modafinil-induced inhibition on IGABA was partly removed.Conclusion Modafinil is a new central noradrenergic receptor agonist in the treatment of narcolepsy. Unlike established psychostimulants, the effects of modafinil on GABA neurons are not straightforward,The protection of modafinil may be via modulating ATP sensitive potassium channel activation,at least in part mediated by KATP channel.更多还原