Effects of phenytoin and gabapentin on veratridine-induced epileptiform discharge in rats' hippocampal CA1 neurones / 解放军医学杂志

ABSTRACT

Objective To observe the effects of phenytoin and gabapentin in therapeutic dosage on low-dose veratridine-induced epileptiform discharge in rats' hippocampal CA1 neurons,and explore the involved mechanisms.Methods By means of whole-cell patch clamp technique,the epileptiform discharge model of rats' hippocampal CA1 neurons was constructed with extracellular perfusion of 0.5?mol/L veratridine,and the model should be regarded as successfully estabilshed if bursting discharge emerged within 30min perfusion.The effects of phenytoin(2.5,5,10 and 15?mol/L) and gabapentin(2.5,5 and 10?mol/L) on the epileptiform activity were observed under the voltage-clamp configuration,and the current changes for 1 hour in CA1 neurons was also observed.Results Nine-sixteen minutes after veratridine perfusion,the huge,rhythmic slow oscillation emerged,with 100～200Hz high-frequency discharge,in the hippocampal CA1 neurons,which was similar to the paroxysmal depolarization shifts(PDS),implying that the epileptiform activity was reproduced.Therapeutic dose of phenytoin blocked the veratridine-induced epileptiform activity.The bursting interval of the epileptiform activity was prolonged along with the increased phenytoin concentration,and the duration of bursting was not shortened.1h current decreased gradually in the generation of veratridine-induced epileptiform activity.Therapeutic dose of gabapentin did not block the epileptiform activity in this model.Conclusions In the epileptiform discharge model of rats' hippocampal CA1 neurons,phenytoin can block the epileptic activity in a dose-dependent manner,and the effect may be related to the inhibition of 1h currents.Gabapentin shows no influence on the epileptiform activity,and the possible mechanism may be its ineffectiveness to the persistent sodium currents,and vertridine-induced epileptiform activity does not enhance the 1h currents.