Zhorov Boris S
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, RAS, St. Petersburg, Russia.
Handb Exp Pharmacol. 2018;246:251-269. doi: 10.1007/164_2017_44.
X-ray and cryo-EM structures of tetrameric and pseudo-tetrameric P-loop channels are used to elaborate homology models of mammalian voltage-gated sodium channels with drugs and neurotoxins. Such models integrate experimental data, assist in planning new experiments, and may facilitate drug design. This chapter outlines sodium channel models with local anesthetics, anticonvulsants, and antiarrhythmics, which are used to manage pain and treat sodium channelopathies. Further summarized are sodium channel models with tetrodotoxin, mu-conotoxins, batrachotoxin, scorpion toxins, and insecticides. Possible involvement of sodium ions in the action of some ligands is discussed.
利用四聚体和假四聚体P环通道的X射线和冷冻电镜结构来构建含有药物和神经毒素的哺乳动物电压门控钠通道的同源模型。此类模型整合了实验数据,有助于规划新的实验,并可能促进药物设计。本章概述了含有局部麻醉药、抗惊厥药和抗心律失常药的钠通道模型,这些药物用于管理疼痛和治疗钠通道病。还总结了含有河豚毒素、μ-芋螺毒素、箭毒蛙毒素、蝎毒素和杀虫剂的钠通道模型。讨论了钠离子在某些配体作用中的可能参与情况。