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塔氏毒蛛β毒素 1(To1)对钠通道亚型的电生理特性分析。

Electrophysiological characterization of Tityus obscurus β toxin 1 (To1) on Na-channel isoforms.

机构信息

Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas, Universidade de Brasília, Brasília, Distrito Federal, Brazil.

Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas, Universidade de Brasília, Brasília, Distrito Federal, Brazil; Instituto Federal de Educação, Ciência e Tecnologia de Brasília, Campus Ceilândia, Brasília, Distrito Federal, Brazil.

出版信息

Biochim Biophys Acta Biomembr. 2019 Jan;1861(1):142-150. doi: 10.1016/j.bbamem.2018.08.005. Epub 2018 Aug 14.

Abstract

To1, previously named Tc49b, is a peptide neurotoxin isolated from venom of the scorpion Tityus obscurus that is responsible for lethal human poisoning cases in the Brazilian Amazonian region. Previously, To1 was shown to be lethal to mice and to change Na permeation in cerebellum granular neurons from rat brain. In addition, To1 did not affect Shaker B K channels. Based on sequence similarities, To1 was described as a β-toxin. In the present work, To1 was purified from T. obscurus venom and submitted to an electrophysiological characterization in human and invertebrate Na channels. The analysis of the electrophysiological experiments reveal that To1 enhances the open probability at more negative potentials of human Na 1.3 and 1.6, of the insect channel BgNa1 and of arachnid VdNa1 channel. In addition, To1 reduces the peak of Na currents in some of the Nas tested. These results support the classification of the To1 as a β-toxin. A structure and functional comparison to other β-toxins that share sequence similarity to To1 is also presented.

摘要

To1,以前称为 Tc49b,是一种从蝎子 Tityus obscurus 的毒液中分离出来的肽神经毒素,它是导致巴西亚马逊地区人类致命中毒的罪魁祸首。以前的研究表明,To1 对老鼠具有致死性,并改变了大鼠脑小脑颗粒神经元中的 Na 通透性。此外,To1 不影响 Shaker B K 通道。基于序列相似性,To1 被描述为一种β-毒素。在本工作中,To1 从 T. obscurus 毒液中纯化出来,并在人源和无脊椎动物 Na 通道中进行了电生理特性分析。电生理实验分析表明,To1 增强了人源 Na 1.3 和 1.6 通道、昆虫通道 BgNa1 和蛛形纲 VdNa1 通道在更负的电位下的开放概率。此外,To1 还降低了部分 Nas 通道的 Na 电流峰值。这些结果支持将 To1 归类为β-毒素。还呈现了与 To1 具有序列相似性的其他β-毒素的结构和功能比较。

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