Cestèle S, Catterall W A
Department of Pharmacology, University of Washington, WA 98195-7280, Seattle, USA.
Biochimie. 2000 Sep-Oct;82(9-10):883-92. doi: 10.1016/s0300-9084(00)01174-3.
Voltage-gated sodium channels are the molecular targets for a broad range of neurotoxins that act at six or more distinct receptor sites on the channel protein. These toxins fall into three groups. Both hydrophilic low molecular mass toxins and larger polypeptide toxins physically block the pore and prevent sodium conductance. Alkaloid toxins and related lipid-soluble toxins alter voltage-dependent gating of sodium channels via an allosteric mechanism through binding to intramembranous receptor sites. In contrast, polypeptide toxins alter channel gating by voltage sensor trapping through binding to extracellular receptor sites. The results of recent studies that define the receptor sites and mechanisms of action of these diverse toxins are reviewed here.
电压门控钠通道是多种神经毒素的分子靶点，这些毒素作用于通道蛋白上六个或更多不同的受体位点。这些毒素可分为三类。亲水性低分子量毒素和较大的多肽毒素都会物理性地阻塞孔道并阻止钠电导。生物碱毒素及相关脂溶性毒素通过与膜内受体位点结合，经由变构机制改变钠通道的电压依赖性门控。相比之下，多肽毒素通过与细胞外受体位点结合，利用电压传感器捕获来改变通道门控。本文综述了近期确定这些不同毒素的受体位点和作用机制的研究结果。
