The changes of ERG channel expression after administration of antiepileptic drugs in the Hippocampus of epilepsy gerbil model

Abstract

[한글]

[영문]Ether-a-go-go (ERG) K+ channel is a channel of potassium inward rectification. ERG channelopathy can induce sudden cardiac death, and channelopathy related with ERG may be a cause of sudden unwanted death. The purpose of our study is to assess the effect of AED on the expression of ERG K+ channel in the hippocampus using seizure resistant (SR) and seizure sensitive (SS) gerbils.Four kinds of drugs were used in this study; Topiramate, Lamotrigine, Valproate and Carbamazepine. Each AED was injected in seven SS and SR gerbils, and AEDs were injected total 28 SS gerbils and 28 SR gerbils. For comparing the effect of AEDs, normal saline was injected at 7 SS gerbils and 7 SR gerbils. Immunoreactivity for ERG K+ channels was checked and its quantitative analysis was performed using the western blot. Hippocampal paired pulse response was checked in SS gerbils and AED injected SS gerbils. In principal neuron of hippocampus, immunoreactivity for ERG channel was significantly decreased after administration of AEDs in SS and SR gerbils comparing to SS and SR gerbils which were given saline (P<0.05). The expression of ERG channel was significantly decreased in AEDs treated SS and SR gerbil rather than the saline injected SS and SR gerbil in Western blot of hippocampus (P<0.05). After administration of AEDs, seizure activities were not observed in SS gerbils. Compared to saline treated SR and SS gerbils, population spike in response to the second stimulus disappeared, thus population spike amplitude ratio was significantly reduced to zero in both SR and SS gerbils. According to our results, AEDs reduced the expression of ERG potassium channel in the hippocampus of the SR and SS gerbils. And, AEDS mainly influenced on the principal neuron of hippocampus.