Sigworth F J, Spalding B C
Nature. 1980 Jan 17;283(5744):293-5. doi: 10.1038/283293a0.
Tetrodotoxin (TTX) and saxitoxin (STX) are extremely potent poisons that prevent nerve and muscle cells from producing action potentials by blocking sodium channels. If the channels are modified by reagents that act on carboxyl groups, however, both the binding of these toxins and their effect on the action potential are reduced. One such reagent, trimethyloxonium ion (TMO) converts channels into a form that is not blocked by TTX concentrations 10(5) times greater than its normal Kd (ref. 6). Most such chemical modifications of sodium channels also reduce the measured membrane sodium current, but it has not been known whether such reductions were due to a change in the number of channels, in permeability properties, or in gating properties. We now report that TMO-modified, TTX-resistant sodium channels have a smaller single-channel conductance (gamma) with a more linear instantaneous current-voltage relationship than that of normal channels, and that the measured reduction in gamma accounts for all of the decrease in sodium current after TMO treatment. This change in sodium channel permeability properties can be explained by the removal of a fixed negative charge near the outside of the channel.
河豚毒素（TTX）和石房蛤毒素（STX）是极具毒性的毒物，它们通过阻断钠通道来阻止神经和肌肉细胞产生动作电位。然而，如果通道被作用于羧基的试剂修饰，这些毒素的结合及其对动作电位的影响都会降低。一种这样的试剂，三甲基氧鎓离子（TMO）能将通道转化为一种形式，在这种形式下，比其正常解离常数（参考文献6）高10^5倍的TTX浓度也不会对其产生阻断作用。钠通道的大多数此类化学修饰也会降低测得的膜钠电流，但尚不清楚这种降低是由于通道数量的变化、通透性特性的变化还是门控特性的变化。我们现在报告，经TMO修饰的、对TTX有抗性的钠通道具有比正常通道更小的单通道电导（γ），且其瞬时电流-电压关系更线性，并且测得的γ降低解释了TMO处理后钠电流的所有下降。钠通道通透性特性的这种变化可以通过去除通道外部附近的一个固定负电荷来解释。
