Anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, in rat models of epilepsy
Article first published online: 29 JAN 2009
2008 British Pharmacological Society
British Journal of Pharmacology
Volume 154, Issue 5, pages 1116–1124, July 2008
How to Cite
Zhao, R., Zhang, X.-Y., Yang, J., Weng, C.-C., Jiang, L.-L., Zhang, J.-W., Shu, X.-Q. and Ji, Y.-H. (2008), Anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, in rat models of epilepsy. British Journal of Pharmacology, 154: 1116–1124. doi: 10.1038/bjp.2008.156
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received December 11, 2007, Revised January 15, 2008, Accepted March 27, 2008)
- BmK IT2;
- intrahippocampal injection;
- status epilepticus;
- epileptic seizures;
- sodium channels
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