Catterall W A, Ray R
J Supramol Struct. 1976;5(3):397-407. doi: 10.1002/jss.400050312.
Four neurotoxins that activate the action potential Na+ionophore of electrically excitable neuroblastoma cells interact with two distinct classes of sites, one specific for the alkaloids veratridine, batrachotoxin, and aconitine, and the second specific for scorpion toxin. Positive heterotropic cooperativity is observed between toxins bound at these two classes of sites. Tetrodotoxin, a specific inhibitor of the action potential Na+ current, inhibits activation by each of these toxins in a noncompetitive manner (KI=4-8 nM). These results suggest the existence of three functionally separable components of the action potential Na+ionophore: two regulatory components which bind activating neurotoxins and interact allosterically in controlling the activity of a third ion-transport component, which binds tetrodotoxin. The dissociation constant for scorpion toxin binding is increased 10-fold by depolarization of the cells with K+, suggesting that the scorpion toxin binding site is located on a voltage-sensitive regulatory component of the ionophore.
四种能激活电兴奋性神经母细胞瘤细胞动作电位钠离子载体的神经毒素与两类不同的位点相互作用，一类对生物碱藜芦碱、箭毒蛙毒素和乌头碱具有特异性，另一类对蝎毒素具有特异性。在这两类位点结合的毒素之间观察到正性异促协同作用。河豚毒素是动作电位钠电流的特异性抑制剂，它以非竞争性方式抑制这些毒素中的每一种的激活作用（抑制常数KI = 4 - 8 nM）。这些结果表明，动作电位钠离子载体存在三个功能上可分离的组分：两个调节性组分，它们结合激活神经毒素并在控制第三个离子转运组分的活性时发生变构相互作用，第三个离子转运组分结合河豚毒素。用钾离子使细胞去极化会使蝎毒素结合的解离常数增加10倍，这表明蝎毒素结合位点位于离子载体的电压敏感调节性组分上。
