Anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, in rat models of epilepsy.

Abstract

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 microg in 2 microl) 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.

• Authors: R Zhao, X-Y Zhang, J Yang, C-C Weng, L-L Jiang, J-W Zhang, X-Q Shu, Y-H Ji
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 154 Issue 5 Pg. 1116-24 (Jul 2008) ISSN: 0007-1188 [Print] England
• PMID: 18587450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• BmK IT2 scorpion toxin
• Proto-Oncogene Proteins c-fos
• Scorpion Venoms
• Sodium Channels
• Pilocarpine
• Lithium Chloride
• Pentylenetetrazole

Topics

• Action Potentials
• Animals
• Anticonvulsants (administration & dosage, pharmacology)
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Electroencephalography
• Hippocampus (drug effects, metabolism)
• Lithium Chloride
• Male
• Pentylenetetrazole
• Pilocarpine
• Proto-Oncogene Proteins c-fos (metabolism)
• Rats
• Rats, Sprague-Dawley
• Scorpion Venoms (administration & dosage, pharmacology)
• Seizures (chemically induced, metabolism, prevention & control)
• Sodium Channels (drug effects, metabolism)