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.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Zhao R,Zhang XY,Yang J,Weng CC,Jiang LL,Zhang JW,Shu XQ,Ji YHdoi
10.1038/bjp.2008.156subject
Has Abstractpub_date
2008-07-01 00:00:00pages
1116-24issue
5eissn
0007-1188issn
1476-5381pii
bjp2008156journal_volume
154pub_type
杂志文章abstract：:1. The kinetics of glycine-sensitive, N-methyl-D-aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique. 2. The degree of fast NMDA-receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 nM to ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13556.x
更新日期：1993-05-01 00:00:00
abstract：:1. Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a...
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pub_type： 杂志文章
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doi：10.1111/j.1476-5381.1989.tb11894.x
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0703089
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pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb09862.x
更新日期：1991-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07919.x
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pub_type： 杂志文章
doi：10.1111/bph.12137
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doi：10.1038/sj.bjp.0705908
更新日期：2004-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17053.x
更新日期：1994-11-01 00:00:00
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pub_type： 杂志文章
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更新日期：1995-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2014-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15470.x
更新日期：1996-06-01 00:00:00
abstract：:1. We have determined which cytokines induce and modulate the production of the chemokine interleukin-8 (IL-8) by the human colonic epithelial cell line HT-29. 2. Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin-1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF-alpha...
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更新日期：1996-09-01 00:00:00
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pub_type： 杂志文章
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更新日期：1994-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：1981-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705732
更新日期：2004-05-01 00:00:00
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doi：10.1111/j.1476-5381.1994.tb13110.x
更新日期：1994-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16384.x
更新日期：1995-09-01 00:00:00
abstract：:1. The inhibitory effect of caffeine on the calcium channel current was investigated in cultured myometrial cells isolated from pregnant rats. 2. Caffeine inhibited the calcium channel current elicited from a holding potential of -70 mV in a concentration-dependent manner. The IC50 was estimated to be 35 mM. 3. The ca...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12622.x
更新日期：1989-10-01 00:00:00
