Morello R S, Begenisich T, Yeh J Z
J Pharmacol Exp Ther. 1984 Jul;230(1):156-61.
The actions of phenytoin (DPH) on sodium channels of squid giant axons were investigated. DPH suppressed the sodium current whether it was applied internally or externally. When DPH was applied externally, its potency depended upon the pH of the external solution. Similarly, when DPH was applied internally, its potency depended on the pH of the internal solution. The potency of DPH increased when the pH of the solution was lowered and the potency was relatively insensitive to pH changes in the solution on the opposite side of the membrane. These results suggest that the weak acid DPH, that exists at physiological pH values in both anionic and neutral forms, acts as a neutral molecule. Our results are reasonably well described by a model wherein one neutral DPH molecule interacts with and blocks one sodium channel. We find an equilibrium constant for the interactions with normal axons to be about 57 microM.
研究了苯妥英（DPH）对鱿鱼巨轴突钠通道的作用。无论将DPH施加于内部还是外部，它都能抑制钠电流。当外部施加DPH时，其效力取决于外部溶液的pH值。同样，当内部施加DPH时，其效力取决于内部溶液的pH值。当溶液的pH值降低时，DPH的效力增加，并且该效力对膜另一侧溶液中的pH变化相对不敏感。这些结果表明，在生理pH值下以阴离子和中性形式存在的弱酸DPH作为中性分子起作用。我们的结果通过一个模型得到了合理的良好描述，其中一个中性DPH分子与一个钠通道相互作用并阻断该通道。我们发现与正常轴突相互作用的平衡常数约为57 microM。
