Site-3 toxins and cardiac sodium channels
Site-3 toxins and cardiac sodium channels
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DOI：
10.1016/j.toxicon.2006.09.017
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发表时间：
2007-02-01
期刊：
影响因子：
2.8
通讯作者：
Sheets, Michael F.
中科院分区：
文献类型：
--
作者：
Hanck, Dorothy A.;Sheets, Michael F.
位点3毒素是来自蝎子、海葵和蜘蛛的小多肽毒液，其以高特异性结合电压门控Na通道的细胞外表面。在结合到结构域IV中的S4片段附近的位点后，毒素引起正常快速失活转变的破坏，导致可兴奋组织（包括心肌和骨骼肌和神经的那些）的动作电位的显著延长。在这篇综述中，我们讨论了毒素和Na通道的残基之间的特异性结合相互作用，以及Na通道动力学行为的特异性修饰导致快速失活的变化，主要是从海葵毒素和心脏Na通道（Na（v）1.5）的研究中推导出的相互作用。我们还说明了有用的网站3毒素在研究改变钠通道行为的药物修饰。(c)2006爱思唯尔有限公司保留所有权利。
Site-3 toxins are small polypeptide venoms from scorpions, sea anemones, and spiders that bind with a high specificity to the extracellular surface of voltage-gated Na channels. After binding to a site near the S4 segment in domain IV the toxin causes disruption of the normal fast inactivation transition resulting in a marked prolongation of the action potentials of excitable tissues including those of cardiac and skeletal muscle and nerve. In this review we discuss the specific binding interactions between residues of the toxin and those of the Na channel, and the specific modification of Na channel kinetic behavior leading to a change in fast inactivation focusing on interactions deduced primarily from the study of sea anemone toxins and the cardiac Na channel (Na(v)1.5). We also illustrate the usefulness of site-3 toxins in the study of altered Na channel behavior by drug-modification. (c) 2006 Elsevier Ltd. All rights reserved.