The tetrodotoxin receptor of voltage-gated sodium channels--perspectives from interactions with micro-conotoxins.
The tetrodotoxin receptor of voltage-gated sodium channels--perspectives from interactions with micro-conotoxins.
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DOI：
10.3390/md8072153
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发表时间：
2010-07-13
期刊：
影响因子：
5.4
通讯作者：
Olivera BM
中科院分区：
文献类型：
--
作者：
French RJ;Yoshikami D;Sheets MF;Olivera BM
神经毒素受体位点1位于电压门控钠通道（VGSC）传导孔的外前庭，其功能首先通过其结合含胍试剂河豚毒素（TTX）和石房蛤毒素（STX）的能力来定义。随后的研究表明，肽μ-芋螺毒素竞争结合位点1。所有这些天然抑制剂在结合时以全或无的方式阻断单钠通道。随着越来越多的μ-芋螺毒素的发现，以及许多衍生物的合成，观察到的通道和这些不同配体之间的相互作用变得更加复杂。某些μ-芋螺毒素衍生物部分地而不是完全地阻断单通道电流，从而能够证明结合的毒素与通道的电压传感器之间的相互作用。最近，相对小的μ-芋螺毒素KIIIA（16个氨基酸）及其变体已显示与TTX同时结合，并表现出与TTX的协同和拮抗相互作用。这些相互作用提出了新的药理学可能性，并对VGSC与这些毒素的结合复合物的可能结构提出了新的限制。
Neurotoxin receptor site 1, in the outer vestibule of the conducting pore of voltage-gated sodium channels (VGSCs), was first functionally defined by its ability to bind the guanidinium-containing agents, tetrodotoxin (TTX) and saxitoxin (STX). Subsequent studies showed that peptide μ-conotoxins competed for binding at site 1. All of these natural inhibitors block single sodium channels in an all-or-none manner on binding. With the discovery of an increasing variety of μ-conotoxins, and the synthesis of numerous derivatives, observed interactions between the channel and these different ligands have become more complex. Certain μ-conotoxin derivatives block single-channel currents partially, rather than completely, thus enabling the demonstration of interactions between the bound toxin and the channel’s voltage sensor. Most recently, the relatively small μ-conotoxin KIIIA (16 amino acids) and its variants have been shown to bind simultaneously with TTX and exhibit both synergistic and antagonistic interactions with TTX. These interactions raise new pharmacological possibilities and place new constraints on the possible structures of the bound complexes of VGSCs with these toxins.
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结合毒素是钠通道外侧前庭中局部pH和静电电位的传感器。
影响因子：
3.8
作者：
Hui, Kwokyin;McIntyre, Deane;French, Robert J
通讯作者：
French, Robert J
影响因子：
2.9
作者：
BECKER, S;PRUSAKSOCHACZEWSKI, E;FRENCH, RJ
通讯作者：
FRENCH, RJ
DOI：
10.4161/chan.3.1.7500
发表时间：
2009-01
期刊：
Channels (Austin, Tex.)
影响因子：
--
作者：
Zhang MM;McArthur JR;Azam L;Bulaj G;Olivera BM;French RJ;Yoshikami D
通讯作者：
Yoshikami D
影响因子：
3.3
作者：
Choudhary, Gaurav;Aliste, Marcela P.;Dudley, Samuel C., Jr.
通讯作者：
Dudley, Samuel C., Jr.
影响因子：
16.2
作者：
French, RJ;PrusakSochaczewski, E;Horn, R
通讯作者：
Horn, R