Werkman T R, Gustafson T A, Rogowski R S, Blaustein M P, Rogawski M A
Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Mol Pharmacol. 1993 Aug;44(2):430-6.
The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-K alpha (TsTX-K alpha) and Dendroaspis angusticeps (snake) toxin dendrotoxin (alpha-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, alpha-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-K alpha produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-K alpha did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-K alpha blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-K alpha the blocking potency of alpha-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. alpha-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-K alpha, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-K alpha and alpha-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites.
研究了两种非同源钾通道毒素——巴西金幽灵蝎毒素tityustoxin-Kα（TsTX-Kα）和绿曼巴蛇毒素树眼镜蛇毒素（α-DTX）对转染表达Kv1.2钾通道的B82成纤维细胞钾电流的相互作用。如先前所示，α-DTX是钾电流的强效阻滞剂（解离常数Kd为2.8 nM）。重组TsTX-Kα对电流产生类似的阻滞作用，但效力强1个数量级（Kd为0.21 nM）。TsTX-Kα不影响电流的动力学特性或其激活的电压依赖性。采用膜片钳全细胞记录和细胞贴附式记录进行的实验表明，TsTX-Kα通过结合细胞外位点来阻断钾通道。在存在TsTX-Kα的情况下，α-DTX的阻滞效力降低，而同样能阻断该通道的4-氨基吡啶的效力不受影响。α-DTX使TsTX-Kα的浓度-反应曲线向右移动，其幅度可通过两种肽毒素存在竞争性相互作用的模型得到合理预测。我们得出结论，TsTX-Kα和α-DTX通过结合相同或密切相关的位点来阻断Kv1.2钾通道。
