用蜘蛛毒素靶向钠通道中的电压传感器。
Targeting voltage sensors in sodium channels with spider toxins.
机构信息
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 USA.
出版信息
Trends Pharmacol Sci. 2010 Apr;31(4):175-82. doi: 10.1016/j.tips.2009.12.007. Epub 2010 Jan 25.
Abstract
Voltage-activated sodium (Nav) channels are essential in generating and propagating nerve impulses, placing them amongst the most widely targeted ion channels by toxins from venomous organisms. An increasing number of spider toxins have been shown to interfere with the voltage-driven activation process of mammalian Nav channels, possibly by interacting with one or more of their voltage sensors. This review focuses on our existing knowledge of the mechanism by which spider toxins affect Nav channel gating and the possible applications of these toxins in the drug discovery process.
摘要
电压门控钠离子通道（Nav）在产生和传播神经冲动中起关键作用，使其成为毒液生物毒素靶向的最广泛的离子通道之一。越来越多的蜘蛛毒素已被证明可通过与一个或多个电压传感器相互作用来干扰哺乳动物 Nav 通道的电压驱动激活过程。本综述重点介绍了我们目前对蜘蛛毒素影响 Nav 通道门控机制的了解，以及这些毒素在药物发现过程中的可能应用。
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2
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