新型黄蜂毒素可区分神经元钠通道和心脏钠通道。

Novel wasp toxin discriminates between neuronal and cardiac sodium channels.

作者信息

Kinoshita E, Maejima H, Yamaoka K, Konno K, Kawai N, Shimizu E, Yokote S, Nakayama H, Seyama I

机构信息

Department of Physiology, School of Medicine, Hiroshima University, Kasumi 1-2-3, Hiroshima 734-8551, Japan.

出版信息

Mol Pharmacol. 2001 Jun;59(6):1457-63.

PMID:11353806

Abstract

Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that beta-PMTX modifies rat brain type II Na+ channel alpha-subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart alpha-subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by beta-PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of beta-PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+ channels.

摘要

蛛蜂毒素（PMTXs）源自独居黄蜂的毒液，已知其能促进龙虾神经肌肉接头处的突触传递，最近一项针对大鼠三叉神经元的进一步研究表明，该毒素可减缓钠离子通道失活，而不改变激活过程。在此我们报告，β - PMTX可修饰在人胚肾细胞中表达的大鼠脑II型钠离子通道α亚基（rBII），但在相似浓度下对大鼠心脏α亚基（rH1）无作用。我们构建了一系列rBII和rH1钠离子通道的嵌合突变体，并比较了β - PMTX对稳态钠电流的修饰作用。我们发现，在D4S3 - S4胞外环中，rBII的Glu - 1616与rH1的Gln - 1615之间单个氨基酸的差异，对β - PMTX的作用至关重要。PMTXs是由13个氨基酸组成的小肽，有望成为探索钠离子通道新功能部分的潜在工具。