Polc P, Jahromi S S, Facciponte G, Pelletier M R, Zhang L, Carlen P L
Department of Medicine (Neurology), Playfair Neuroscience Unit, Toronto Hospital Research Institute, Ontario, Canada.
Neuroreport. 1995 Jul 31;6(11):1549-52. doi: 10.1097/00001756-199507310-00021.
We examined the effects of the benzodiazepine antagonist, flumazenil, on epileptiform discharges evoked in the hippocampal CA1 region in vitro. Application of 100 nM flumazenil did not affect normal synaptic responses; however, flumazenil did depress epileptiform discharges induced by 8 mM [K+]o. Epileptiform discharges induced by the GABAA channel antagonist picrotoxin or by the K+ channel blocker 4-aminopyridine were unaffected. Application of the high-affinity, low-efficacy benzodiazepine partial inverse agonist, Ro 19-4603, blocked the anticonvulsant effect of flumazenil, indicating that this action of flumazenil is mediated at a benzodiazepine binding site located on the GABAA receptor. A likely explanation of the present results is that flumazenil antagonizes the action of an endogenous benzodiazepine inverse agonist, which is released during epileptiform discharges evoked in high K+ ACSF.
我们研究了苯二氮䓬拮抗剂氟马西尼对体外培养的海马CA1区诱发的癫痫样放电的影响。应用100 nM氟马西尼不影响正常的突触反应；然而，氟马西尼确实抑制了由8 mM [K⁺]o诱导的癫痫样放电。由GABAA通道拮抗剂印防己毒素或K⁺通道阻滞剂4-氨基吡啶诱导的癫痫样放电不受影响。应用高亲和力、低效价的苯二氮䓬部分反向激动剂Ro 19-4603可阻断氟马西尼的抗惊厥作用，表明氟马西尼的这一作用是通过位于GABAA受体上的苯二氮䓬结合位点介导的。对目前结果的一个可能解释是，氟马西尼拮抗了内源性苯二氮䓬反向激动剂的作用，该反向激动剂在高钾人工脑脊液诱发的癫痫样放电过程中释放。
