Sıçanlarda Penisilin G ile oluşturulan epilepsi modelinde ATP bagımlık (KATP) kanal agonist ve antagonistlerinin etkileri

Epilepsy is a neurological disease having a high incidence in the world that characterized with abrupt, extreme, rhythmic, abnormal elecrtical discharges. It is characterized with hypersynchronization occuring due to disturbance of equillibrium between inhibitory and excitatory systems and shifting the electrical activity towards the excitator side. Although molecular mechanism of seizures are not fully understood, functions of membrane channels are not known well. ATP dependent potassium channels have been shown to have a role in control of seizures. ATP dependent potassium channels regulate excitatory neurotransmitter release of neurons. In control of seizure, ATP dependent potassium channels play a very important role and found in most of the tissues. The physiological roles of ATP dependent potassium channels have been demonstrated in cardiac myocytes, pancreatic β cells and muscle cells. KATP channels is effective in seizure and control of chronic epilepsy models that have been shown in many studies. In these studies, it is found that KATP opener increase seizure threshold. Aim of the study is to research the effects of KATP channel agonists (opener) and antagonists (blocker) in the penicillin model of experimental epilepsy. Wistar albino male rats were used in this study. Groups were divided into three main groups which were; control, before-seizure and during seizure groups. Epilepsy was produced by application of 500IU 2.5 µl penisilinin intracortically. In the first step of this study, the effective dose of bepridil (ATP dependent mitochondrial potassium channel opener) and P1075 (sarcolemmal KATP opener ) were determined. Bepridil, P1075, HMR1098 (sarcolemmal KATP blocker-3mg / kg), 5HD (mitochondrial KATP blocker-10mg / kg) were given before seizure and during seizure. The effect of each drug on the apperance of the frequency and amplitude of epileptic spike were determined. Differences within groups were tested by one way ANOVA. LSD test was used as a post hoc test. P values which were smaller than 0,05 were accepted as significant. P1075 0.1mg/kg delayed seizure when it was applied before seizure (p < 0.05). When bepridil applied 1mg/kg in dose before and during seizure, it decreased spike frequency compared to control (p < 0.05). P1075 in 0.1 mg / kg dose applied before seizure and during seizure decreased spike frequency significantly compared to control group. On the other hand, P1075 0.5 mg / kg in dose applied during seizure and 0.1 mg / kg in dose applied before seizure ended seizure earlier than the control group. HMR 1098 applied before seizure started seizure earlier in respect to control. In 5HD and HMR 1098 groups, there were no significant differences in latency. When 5HD and HMR 1098 applied before seizure and during seizure they increased spike frequency compared to control group (p < 0.05). As a result, KATP channel blockers in experimental penicillin model of epilepsy, increase spike wave frequency, otherwise KATP channel opener P1075 and bepridil decrease spike frequency (p < 0.05). At the same time while Bepridil and P1075 delayed the seizure. HMR 1098 and 5HD caused early apperance of seizure spike following penicillin treatment. As a result both sarcolemmal and mitochondrial openers have protective effect, on the other side, blockers have deleterous effect in the epileptic activity and its duration. Keywords: Epilepsy, mito KATP, sarc KATP, Bepridil, 5-HD, P-1075, HMR-1098