一种新型的阻断小电导钙激活钾通道的蝎毒素。

A novel scorpion toxin blocking small conductance Ca2+ activated K+ channel.

作者信息

Xu Chen-Qi, He Lin-Lin, Brône Bert, Martin-Eauclaire Marie-France, Van Kerkhove Emmy, Zhou Zhuan, Chi Cheng-Wu

机构信息

Institute of Neuroscience, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.

出版信息

Toxicon. 2004 Jun 15;43(8):961-71. doi: 10.1016/j.toxicon.2004.01.018.

DOI:10.1016/j.toxicon.2004.01.018

PMID:15208029

Abstract

Small conductance calcium activated potassium channels (SK) are crucial in the regulation of cell firing frequency in the nervous system and other tissues. In the present work, a novel SK channel blocker, designated BmSKTx1, was purified from the scorpion Buthus martensi Karsh venom. The sequence of the N-terminal 22 amino acid residues was determined by Edman degradation. Using this sequence information, the full-length cDNA and genomic gene of BmSKTx1 were cloned and sequenced. By these analyses, BmSKTx1 was found to be a peptide composed of 31 amino acid residues with three disulfide bonds. It shared little sequence homology with other known scorpion alpha-KTxs but showed close relationship with SK channel blockers in the phylogenetic tree. According to the previous nomenclature, BmSKTx1 was classified as alpha-KTx14.1. We examined the effects of BmSKTx1 on different ion channels of rat adrenal chromaffin cells (RACC) and locust dorsal unpaired median (DUM) neurons. BmSKTx1 selectively inhibited apamin-sensitive SK currents in RACC with Kd of 0.72 microM and Hill coefficient of 2.2. And it had no effect on Na+, Ca2+, Kv, and BK currents in DUM neuron, indicating that BmSKTx1 was a selective SK toxin.

摘要

小电导钙激活钾通道（SK）在调节神经系统和其他组织中的细胞放电频率方面至关重要。在本研究中，一种名为BmSKTx1的新型SK通道阻滞剂从东亚钳蝎毒液中纯化得到。通过埃德曼降解法测定了其N端22个氨基酸残基的序列。利用该序列信息，克隆并测序了BmSKTx1的全长cDNA和基因组基因。通过这些分析，发现BmSKTx1是一种由31个氨基酸残基组成的肽，具有三个二硫键。它与其他已知的蝎α-KTxs几乎没有序列同源性，但在系统发育树中与SK通道阻滞剂显示出密切关系。根据先前的命名法，BmSKTx1被归类为α-KTx14.1。我们研究了BmSKTx1对大鼠肾上腺嗜铬细胞（RACC）和蝗虫背中无对神经元（DUM）不同离子通道的影响。BmSKTx1以0.72 microM的Kd和2.2的希尔系数选择性抑制RACC中对蜂毒明敏感的SK电流。并且它对DUM神经元中的Na+、Ca2+、Kv和BK电流没有影响，表明BmSKTx1是一种选择性SK毒素。