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Inhibitory effects of recombinant neurotoxin BmK IM on seizures induced by pentylenetetrazol in Rats

何小华 彭方 章军建 李文鑫 曾宪春 刘辉

中华医学杂志(英文版)2003,Vol.116Issue(12):1898-1903,6.
中华医学杂志(英文版)2003,Vol.116Issue(12):1898-1903,6.

Inhibitory effects of recombinant neurotoxin BmK IM on seizures induced by pentylenetetrazol in Rats

Inhibitory effects of recombinant neurotoxin BmK IM on seizures induced by pentylenetetrazol in Rats

何小华 1彭方 2章军建 1李文鑫 3曾宪春 1刘辉1

作者信息

  • 1. Department of Biotechnology, College of Life Science, Wuhan University, Wuhan 430072,China
  • 2. Department of Neurology, Wuhan General Hospital of PLA, Wuhan 430070, China
  • 3. Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan 430070, China
  • 折叠

摘要

Abstract

Objective To elucidate the inhibitory effects of recombinant Chinese scorpion neurotoxin BmK IM on seizures induced by pentylenetetrazol (PTZ) and the possible mechanism.Methods After purifying recombinant BmK IM from an E. coli cell line, its toxicity (both LD50 and minimum lethal dose) on rats was determined. BmK IM was then microinjected into the CA3 region of the right hippocampus and its ability to inhibit the effects of an intraperitoneal injection of PTZ was assessed. The effects of BmK IM on the electrophysiological properties of isolated CA3 pyramidal neurons were then studied using whole-cell patch clamp techniques.Results BmK IM can significantly prolong the latent period of epileptic seizures, decrease the degree of seizures, and decrease the frequency of epileptiform discharges induced by PTZ. At the same time, 24h after injection of BmK IM into the hippocampal tissue, BmK IM significantly reduces the concentration of the neurotransmitter glutamate and alleviates PTZ-induced lesions in the hippocampus. Whole-cell patch clamp recordings indicate that BmK IM inhibits INa of rat hippocampal neurons in a dose-dependent manner. BmK IM significantly shifts the activation curve of INa in a positive direction, indicating that BmK IM enhances the threshold potential of INa.Conclusions BmK IM has significant anti-epileptic properties, and may prove useful as a drug in the therapy of epilepsy. The inhibitory effects of BmK IM on seizures caused by pentylenetetrazol might depend on reductions in the release of presynaptic glutamate via the blocking of Na+ channels.

关键词

scorpion toxin/sodium channel/epilepsy/glutamate/patch-clamp techniques/hippocampus

Key words

scorpion toxin/sodium channel/epilepsy/glutamate/patch-clamp techniques/hippocampus

分类

医药卫生

引用本文复制引用

何小华,彭方,章军建,李文鑫,曾宪春,刘辉..Inhibitory effects of recombinant neurotoxin BmK IM on seizures induced by pentylenetetrazol in Rats[J].中华医学杂志(英文版),2003,116(12):1898-1903,6.

基金项目

This study was supported by the National Nature Science Foundation of China (No. 30200083) and the Hubei Gongguan Project of Science and Technology (No. 2002AA304B09). (No. 30200083)

中华医学杂志(英文版)

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