ω-芋螺毒素MVIIA抑制Sprague-Dawley大鼠杏仁核点燃性癫痫发作。

omega-Conotoxin MVIIA inhibits amygdaloid kindled seizures in Sprague-Dawley rats.

作者信息

Wang Shuang, Ding Meiping, Wu Dengchang, Zhan Jinbiao, Chen Zhong

机构信息

Department of Pharmacology and Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, China.

出版信息

Neurosci Lett. 2007 Feb 14;413(2):163-7. doi: 10.1016/j.neulet.2006.11.049. Epub 2007 Jan 4.

DOI:10.1016/j.neulet.2006.11.049

PMID:17207931

Abstract

omega-Conotoxin MVIIA (omega-CTX MVIIA) is a reversible and potent antagonist of N-type voltage-dependent calcium channels (VDCCs) in neurons. In this study, we evaluated the effect of a fusion form of omega-CTX MVIIA with glutathione S-transferase (GST) on amygdaloid kindled seizures. Intracerebraventricular (i.c.v.) injection of the fusion protein of GST-omega-CTX MVIIA significantly decreased seizure stage and shortened afterdischarge duration and generalized seizure duration in a dose-dependent and time-related manner. In addition, GST-omega-CTX MVIIA significantly increased the GABA levels in the cortex and glycine levels in the brainstem. In contrast, GST alone did not have any effect on seizure behavior or neurochemical levels. These findings firstly demonstrate that the N-type VDCC is a potential therapeutic target for temporal lobe epilepsy. The mechanism of the anticonvulsant function of omega-CTX MVIIA is related to the blockade of N-type VDCC-mediated neurotransmitter release in the brain.

摘要

ω-芋螺毒素MVIIA（ω-CTX MVIIA）是神经元中N型电压依赖性钙通道（VDCC）的一种可逆性强效拮抗剂。在本研究中，我们评估了ω-CTX MVIIA与谷胱甘肽S-转移酶（GST）的融合形式对杏仁核点燃性癫痫发作的影响。脑室内（i.c.v.）注射GST-ω-CTX MVIIA融合蛋白以剂量依赖性和时间相关性方式显著降低癫痫发作阶段，并缩短放电后持续时间和全身性癫痫发作持续时间。此外，GST-ω-CTX MVIIA显著提高了皮质中的GABA水平和脑干中的甘氨酸水平。相比之下，单独的GST对癫痫发作行为或神经化学水平没有任何影响。这些发现首次证明N型VDCC是颞叶癫痫的一个潜在治疗靶点。ω-CTX MVIIA抗惊厥功能的机制与阻断大脑中N型VDCC介导的神经递质释放有关。