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Anticonvulsant effect of BmK IT2, a sodium channel‐specific neurotoxin, in rat models of epilepsy
Author(s) -
Zhao R,
Zhang XY,
Yang J,
Weng CC,
Jiang LL,
Zhang JW,
Shu XQ,
Ji YH
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.156
Subject(s) - pilocarpine , status epilepticus , epilepsy , sodium channel , neurotoxin , anticonvulsant , hippocampal formation , pharmacology , hippocampus , electroencephalography , medicine , electrophysiology , neuroscience , sodium channel blocker , chemistry , pentylenetetrazol , sodium , anesthesia , psychology , organic chemistry
Background and purpose: The sodium channel is a primary target for treating central nervous system disorders such as epilepsy. In this study the anticonvulsant effect of BmK IT2, a sodium channel‐specific neurotoxin, was evaluated in different animal models of epilepsy. Experimental approach: Experiments were performed on freely moving rats made epileptic by administration of either pentylenetetrazole (PTZ) or pilocarpine. BmK IT2 (0.05–0.5 μg in 2 μl) was microinjected into the CA1 area and its effects on PTZ‐induced widespread, seizure‐like behaviour and cortex epileptiform EEG, as well as on pilocarpine‐induced seizure‐like behaviour and c‐Fos expression were studied. Key results: Intrahippocampal application of BmK IT2 dose‐dependently inhibited PTZ‐induced seizure‐like behaviour, and reduced the numbers and duration of the high amplitude and frequency discharges (HAFDs) of the epileptiform EEG component induced by PTZ. Similarly, in the pilocarpine‐induced status epilepticus (SE) model, BmK IT2 significantly prolonged the latency to onset of the SE, reduced the severity of SE and suppressed hippocampal c‐Fos expression during SE. Conclusions and implications: BmK IT2 showed anticonvulsant activity as it inhibited the widespread seizures induced by PTZ and pilocarpine‐induced SE in rats. This activity might be due to the modulation of sodium channels in the hippocampus. Hence, BmK IT2 could be used as a novel tool to explore the molecular and pathological mechanisms of epilepsy with regard to the involvement of sodium channels. British Journal of Pharmacology (2008) 154 , 1116–1124; doi: 10.1038/bjp.2008.156 ; published online 21 April 2008