Israel Mathilde R, Tay Bryan, Deuis Jennifer R, Vetter Irina
Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Adv Pharmacol. 2017;79:67-116. doi: 10.1016/bs.apha.2017.01.004. Epub 2017 Apr 8.
Venomous animals including cone snails, spiders, scorpions, anemones, and snakes have evolved a myriad of components in their venoms that target the opening and/or closing of voltage-gated sodium channels to cause devastating effects on the neuromuscular systems of predators and prey. These venom peptides, through design and serendipity, have not only contributed significantly to our understanding of sodium channel pharmacology and structure, but they also represent some of the most phyla- and isoform-selective molecules that are useful as valuable tool compounds and drug leads. Here, we review our understanding of the basic function of mammalian voltage-gated sodium channel isoforms as well as the pharmacology of venom peptides that act at these key transmembrane proteins.
包括芋螺、蜘蛛、蝎子、海葵和蛇在内的有毒动物,其毒液中已进化出无数成分,这些成分作用于电压门控钠通道的开启和/或关闭,从而对捕食者和猎物的神经肌肉系统造成毁灭性影响。这些毒液肽,无论是通过设计还是偶然发现,不仅极大地促进了我们对钠通道药理学和结构的理解,而且它们还代表了一些最具门和亚型选择性的分子,可用作有价值的工具化合物和药物先导物。在此,我们综述了我们对哺乳动物电压门控钠通道亚型基本功能的理解,以及作用于这些关键跨膜蛋白的毒液肽的药理学。