The effects of ATP –dependent potassium channel (KATP) agonist and antagonists on Penicillin G induced epilepsy model in rats
Küçük Resim Yok
Tarih
2014
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bolu Abant İzzet Baysal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Epilepsi dünyada görülme oranı yüksek olan nörolojik bir hastalıktır. Ani, şiddetli, ritmik, anormal elektriksel deşarjlarla karakterizedir. İnhibitör ve eksitatör sistem arasındaki dengenin eksitatör tarafa bozulması sonucu olusan hipersenkronizasyon ile karakterizedir. Nöbetlerin moleküler mekanizması tam olarak bilinmemesine rağmen nöbetlerin kontrolünde ATP bağımlı potasyum kanallarının rolü olduğu gösterilmiştir. ATP bağımlı potasyum kanalları nöronların eksitator nörotransmitter salınımını düzenler. Nöbetin kontrolünde ATP bağımlı potasyum kanalları çok önemi rol oynar. KATP kanaları birçok dokuda bulunur. Örnegin kardiyak miyositlerde, pankreatik beta hücrelerinde, kas hücrelerinde birçok fizyolojik role sahiptir. Birçok çalşmada kronik epilepsi modellerinde KATP kanallarının nöbet kontrolünde etkili olduğu gösterilmiştir. KATP agonistlerinin nöbet eşiğini arttırdığı ve antagonistlerinin de azalttığı, yapılan çalışmalarla ortaya konmuştur. İstatistiki verilere göre epilepsi hastalığının dişi ve erkek bireylerde görülme oranı eşittir. Çalışmanın amacı KATP kanal agonist (opener) ve antagonistlerinin (bloker) penisilin modeli deneysel epilepsi üzerine etkilerini araştırmaktır. Çalışmada wistar albino cinsi erkek sıçanlar kullanıldı. Kontrol, nöbet öncesi ve nöbet sırası olmak üzere üç ana grup oluşturuldu. Epilepisi 500 IU 2.5 µl penisilinin intrakortikal verilmesi ile oluşturuldu. Çalısmanın birinci aşamasında mitokondriyal KATP açıcısı olan bepridil ve P1075 in etkili dozları saptandı. İkinci aşamada HMR 1098 (sarkolemmal KATP bloker-3 mg / kg ) ve 5HD ( mitokondriyal KATP blokerı-10 mg / kg ) nöbet öncesi ve nöbet sırasında verildi ve epileptik diken dalgaların frekansı ve genlikleri saptandı. Gruplar arasındaki farlılıklar ANOWA ile değerlendirildi. Post hoc testi olarak ise LSD kullanıldı. P < 0.05 değerleri anlamlı olarak kabul edildi. P1075 0.1 mg / kg ve bepridil 10 mg / kg nöbet öncesi uygulandığında nöbeti geciktirmiştir (p < 0.05) . Bepridil nöbet öncesinde ve sırasında 1 mg / kg dozda uygulandığında diken dalga frekansını kontrole göre azaltmıştır (p<0.05). P1075 nöbet öncesinde ve sırasında 0.1 mg / kg dozda diken dalga sayısını kontrol grubuna göre anlamlı olarak azaltmıştır. P1075'in 0.5 mg / kg dozda ise nöbeti erken sonlandırmıştır. 5HD ve HMR 1098 gruplarında nöbete başlama zamanları kontrole göre değişmemiştir. 5HD ve HMR 1098 nöbet öncesinde ve nöbet sırasında uygulandığında diken dalga frekansını kontrole göre artırmıştır (p < 0.05). Bu sonuçlara göre KATP kanal kapatıcısı penisilin modeli deneysel epilepside nöbet şiddetini belirleyen diken dalga sayısını artırırken. KATP kanal açıcısı P1075 ve bepridil diken dalga sayısını azaltmıştır (p < 0.05). Aynı zamanda Bepridil ve P1075 nöbeti geciktirirken HMR 1098 ve 5HD nöbete başlamayı kolaylaştırmıştır. Sonuç olarak Hem sarkolemmal hemde mitokondrial KATP açıcılar epilepsi üzerinde koruyucu etkiye sahipken kapatıcılar ise epileptik aktiviteyi ve süresini artırmıştır. Anahtar Kelimeler: Epilepsy, mito KATP, sarc KATP, Bepridil, 5-HD, P-1075, HMR-1098
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 ? 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
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 ? 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
Açıklama
Fen Bilimleri Enstitüsü, Biyoloji Ana Bilim Dalı
Anahtar Kelimeler
Fizyoloji, Physiology
