Otoom S, Tian L M, Alkadhi K A
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, TX 77204-5515, USA.
Brain Res. 1998 Apr 6;789(1):150-6. doi: 10.1016/s0006-8993(98)00026-2.
This study introduces veratridine-treated brain slices as a new in vitro synaptic-independent model for epileptiform discharge. Studies were performed on the hippocampus in rat brain slices using conventional electrophysiological intracellular recording techniques. Veratridine (0.3 microM) produced a time-dependent blockade of synaptic transmission as indicated by inhibition of the evoked population spike in the region CA1 of the hippocampus. However, in the same slices, intracellularly-evoked single action potentials were converted to epileptiform bursting shortly after exposure to veratridine. Additionally, in the veratridine model, spontaneous epileptiform activity developed after prolonged (more than 45 min) superfusion. The model was utilized to examine the action of two antiepileptic drugs: a sodium channel dependent and a synaptic dependent antiepileptic agents. Therapeutic concentrations of valproic acid (VPA, 10-100 microM) inhibited both evoked and spontaneous bursting induced by veratridine. However, therapeutic concentrations of the synaptic-dependent antiepileptic drug phenobarbital (20-40 microM) failed to inhibit veratridine-induced bursting. These results demonstrate that the veratridine-treated brain slice is a simple and reliable model for studying mechanisms of action and for screening of potential sodium channel-dependent antiepileptic drugs.
本研究引入了藜芦碱处理的脑片作为一种新的用于癫痫样放电的体外非突触模型。使用传统的细胞内电生理记录技术对大鼠脑片的海马体进行了研究。藜芦碱（0.3微摩尔）产生了时间依赖性的突触传递阻断，这通过海马体CA1区诱发群体峰电位的抑制来表明。然而，在同一切片中，细胞内诱发的单个动作电位在暴露于藜芦碱后不久就转变为癫痫样爆发。此外，在藜芦碱模型中，长时间（超过45分钟）灌注后会出现自发性癫痫样活动。该模型被用于研究两种抗癫痫药物的作用：一种是钠通道依赖性抗癫痫药物，另一种是突触依赖性抗癫痫药物。丙戊酸（VPA，10 - 100微摩尔）的治疗浓度抑制了藜芦碱诱发的和自发性爆发。然而，突触依赖性抗癫痫药物苯巴比妥（20 - 40微摩尔）的治疗浓度未能抑制藜芦碱诱发的爆发。这些结果表明，藜芦碱处理的脑片是一个用于研究作用机制和筛选潜在钠通道依赖性抗癫痫药物的简单可靠模型。
