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


METHODS
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.


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
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.
Zhao
R
R
Graduate School of the Chinese Academy of Sciences, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Zhang
X-Y
XY
Yang
J
J
Weng
C-C
CC
Jiang
L-L
LL
Zhang
J-W
JW
Shu
X-Q
XQ
Ji
Y-H
YH
D000200:Action Potentials; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004569:Electroencephalography; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018021:Lithium Chloride; D008297:Male; D010433:Pentylenetetrazole; D010862:Pilocarpine; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D000927:Anticonvulsants; C417087:BmK IT2 scorpion toxin; D016760:Proto-Oncogene Proteins c-fos; D012604:Scorpion Venoms; D015222:Sodium Channels; D010862:Pilocarpine; D018021:Lithium Chloride; D010433:Pentylenetetrazole