Wang G K, Strichartz G R
Mol Pharmacol. 1983 Mar;23(2):519-33.
Several different toxins having specific effects on the kinetics of sodium channels have been isolated from the venoms of two scorpions. A combination of two steps of ion-exchange chromatography has been used to purify these toxins, whose sizes and purities have been assayed by gel filtration, urea/sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and isoelectric focusing. The actions of the toxins and their relative potencies have been determined by studying the modifications they produce in action potential shape, using the sucrose-gap method, and in ionic current kinetics, measured under voltage-clamp, both assays performed on myelinated axons of frogs and toads. The venom of Leiurus quinquestriatus scorpions yielded two active neurotoxins; the major neurotoxin has a mass of approximately 7000 daltons. This major toxin affected the sodium channel inactivation process exclusively, slowing the rates of inactivation as well as preventing complete inactivation from occurring in some of the channels. Such slowed and incomplete sodium inactivation resulted in action potentials that were prolonged, from their usual duration of 5-8 msec to hundreds of milliseconds or even seconds. Five toxins were isolated from the venom of Centruroides sculpturatus Ewing scorpions, all of which also had masses of approximately 7000-7500 daltons. Four of these toxins acted primarily on the activation process of sodium channels, producing a novel increase in sodium permeability upon repolarization of the nerve membrane following a depolarizing pulse, as previously described for the crude venom [Cahalan, M. D. J. Physiol. (Lond.) 244:511-534 (1975)]. These toxins also caused repetitive firing of action potentials in single axons in response to one stimulating pulse, as well as spontaneous impulse firing. A fifth neurotoxin from C. sculpturatus venom had effects similar to those of the L. quinquestriatus toxins, slowing and preventing complete sodium inactivation. The effect of this toxin was slowly removed during external perfusion by Ringer's solution.
从两种蝎子的毒液中分离出了几种对钠通道动力学具有特定作用的不同毒素。采用两步离子交换色谱法对这些毒素进行了纯化，其大小和纯度通过凝胶过滤、尿素/十二烷基硫酸钠/聚丙烯酰胺凝胶电泳和等电聚焦进行了测定。通过研究它们对动作电位形状的改变（使用蔗糖间隙法）以及离子电流动力学（在电压钳制下测量）来确定毒素的作用及其相对效力，这两种测定均在青蛙和蟾蜍的有髓轴突上进行。以色列金蝎的毒液产生了两种活性神经毒素；主要的神经毒素质量约为7000道尔顿。这种主要毒素仅影响钠通道的失活过程，减缓失活速率，并阻止一些通道完全失活。这种缓慢且不完全的钠失活导致动作电位延长，从通常的5 - 8毫秒延长至数百毫秒甚至数秒。从雕刻杀人蝎的毒液中分离出了五种毒素，它们的质量也都约为7000 - 7500道尔顿。其中四种毒素主要作用于钠通道的激活过程，在去极化脉冲后神经膜复极化时使钠通透性产生新的增加，如先前对粗毒液所描述的那样[卡拉汉，M. D. 《生理学杂志》（伦敦）244:511 - 534（1975）]。这些毒素还会导致单个轴突在一个刺激脉冲后产生动作电位的重复发放以及自发冲动发放。来自雕刻杀人蝎毒液的第五种神经毒素具有与以色列金蝎毒素类似的作用，减缓并阻止完全的钠失活。在外部用林格氏液灌注期间，这种毒素的作用会缓慢消除。
