Potassium Channels In Regulation Of Drug Kindling Model And Its Mechanism

Objective: In this study, amygdala kindling model in rats Was established to be used to screen potassium channel modulator that can be used to antiepileptic drugs and then to investigate the possible mechanisms and characteristic of different types of potassium channel modulator on epilepsy. The effects of above-mentioned valid anti-kindled drags on maximal electroshock seizure test (MES) and spontaneous activity of mice were observed. The results are as follows:Mathods: Establish amygdala kindling epilepsy model and to survey the effect of potassium channel modulator on kindling. And using different types of potassium channel modulator instrument drugs to reseach the mechanisms of anti-kinded drugs.Maximal electroshock seizure test (MES) and spontaneous activity of mice are used to study the effect of above-mentioned valid anti-kindled drugs on maximal electroshock and central nervous system(CNS) motor behavior.Results: 1.Amygdala kindling model were established successfully, we found that 1.1. Kushenin 100 (P＜0.01), 200 mg·kg^-1(P＜0.05) can decrease ADD and the combination-administration of kushenin with nicardipine, phenytoin and valproate all at ineffective doses are also observed. The results suggest that combination of kushenin with phenytoin both at ineffective doses can decrease ADD (P＜0.05) but show no effect on Racine's stages. 1.2 Nicorandil 1.0umol×5d can decrease both ADD(P＜0.01) and Racine's stages (P＜0.01) by intracerebroventricular injection. 1.3. Ligustrazine 20,80 mg·kg^-1can decrease ADD (P＜0.05) but show no effect on Racine's stages. 1.4 Scopolamine 2.0,2.5 mg·kg^-1can decrease ADD (P＜0.05) but show no effect on Racine's stages.But amiodarone,sotalol,diazoxide,glibenclamide,anisodamine and scorpion show no effect on ADD and Racine's stages (P＞0.05)。2. Maximal electroshock model showed that compared to isotonic Na chloride ligustrazine 40, 80 rng·kg^-1,kushenin100, 200mg·kg^-1,nicorandil 1.0,5.0mg·kg^-1 can decrease convulsion incidence (P＜0.01 ),but Scopolamine have not statistically significant on convulsion incidence (P＞0.05)。3. The model of spontaneous activity of the mice showed that compared to the control group ligustrazine 40(P＜0.05),80(P＜0.01)mg·kg^-1; kushenin 100 (P＜0.05),200 (P＜0.01) mg·kg^-1;Scopolamine 1.0 (P＜0.05),2.0 mg·kg^-1(P＜0.01) could decrease the number within 5 minutes of spontaneous activity of the mice but nicorandil did not have showed this effect (P＞0.05).Conclusion: 1.Kushenin, the inward rectifyimg potassium channel blocker; ligustrazine, the large-conductance Calcium-activated potassium channels opener; nicorandil, the opener of K_ATP: Scopolamine as the Ach active potassium channels blocker can also decrease kindling. Which demonstrated that above-mentioned potassium ion channel subtype could participate in control kindling mechanisms. Ligustrazine, kushenin, and scopolamine can decrease convulsion incidence of maximal electroshock Which demonstrated that above-mentioned drugs can have effect of acute simple partial seizures. Ligustrazine, kushenin, and scopolamine could decrease the number within 5 minutes of spontaneous activity of the mice Which demonstrated that above-mentioned drugs can product center inhibitory action. This effect and mechanisms of above-mentioned potassium channel modulator anti-kinded is to be identical.