Hanck Dorothy A, Sheets Michael F
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Toxicon. 2007 Feb;49(2):181-93. doi: 10.1016/j.toxicon.2006.09.017. Epub 2006 Sep 27.
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.
3型位点毒素是来自蝎子、海葵和蜘蛛的小多肽毒液，它们以高特异性与电压门控钠通道的细胞外表面结合。毒素与结构域IV中S4片段附近的位点结合后，会导致正常快速失活转变的破坏，从而使可兴奋组织（包括心肌、骨骼肌和神经组织）的动作电位显著延长。在这篇综述中，我们讨论毒素残基与钠通道残基之间的特异性结合相互作用，以及钠通道动力学行为的特异性改变导致快速失活变化的情况，重点关注主要从海葵毒素和心脏钠通道（Na(V)1.5）研究中推断出的相互作用。我们还举例说明了3型位点毒素在通过药物修饰研究钠通道行为改变方面的用途。
