Structural determinants of the affinity of saxitoxin for neuronal sodium channels. Electrophysiological studies on frog peripheral nerve.
Structural determinants of the affinity of saxitoxin for neuronal sodium channels. Electrophysiological studies on frog peripheral nerve.
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石房蛤毒素对神经元钠通道亲和力的结构决定因素。
DOI：
10.1085/jgp.84.2.281
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Strichartz,G
中科院分区：
文献类型：
--
作者：
Strichartz,G
石房蛤毒素（STX）和五种结构相关毒素的效力由它们在青蛙坐骨神经平衡时阻断冲动的能力来确定。效力的顺序（括号中为相对于STX效力的值）为：新-STX（4.5）大于gonyautoxin（GTX）III（1.4）大于STX（1.0）大于GTXII（0.22）大于12 α-二氢STX（0.050）大于12 β-二氢STX（0.0014）。当交换STX和neo-STX的等效力溶液时，被治疗神经中的冲动被暂时过度阻断或阻断不足，从而在动力学上区分neo-STX和STX。STX和GTXIII的交换也出现了类似的现象。没有发现任何一致的证据表明在C8胍处未质子化的STX分子具有任何阻断活性，但STX效力的pH依赖性不能简单地通过滴定该胍基团来描述。pH值和各种取代基对STX效力的影响是由STX分子形式的变化和STX和受体上特定电荷的改变引起的。结果支持一种模型，其中毒素分子结合在两个步骤中; C8胍与阴离子基团的初始结合诱导正常水合酮（在碳12处）的水损失，然后与受体上的亲核基团形成弱共价键。
The potencies of saxitoxin (STX) and of five structurally related toxins were determined by their ability to block impulses at equilibrium in frog sciatic nerve. The order of potency, with values relative to STX potency in parentheses, was: neo-STX (4.5) greater than gonyautoxin (GTX) III (1.4) greater than STX (1.0) greater than GTXII (0.22) greater than 12 alpha-dihydroSTX (0.050) greater than 12 beta-dihydroSTX (0.0014). When equipotent solutions of STX and neo-STX were exchanged, impulses in the treated nerve were transiently overblocked or underblocked, thus kinetically distinguishing neo-STX from STX. Similar phenomena occurred with exchanges of STX and GTXIII. No consistent evidence was found for any blocking activity of STX molecules that were not protonated at the C8 guanidinium, but the pH dependence of STX potency cannot be described simply by the titration of this guanidinium group. The effects of pH and of various substituents on STX potency are accounted for by changes in the molecular forms of STX and by alterations in specific electrical charges on STX and at the receptor. The results support a model in which toxin molecules bind in two steps; initial binding of the C8 guanidinium to an anionic group induces the loss of water from the normally hydrated ketone (at carbon 12), which then forms a weak covalent bond with a nucleophilic group on the receptor.