DIFFERENTIAL-EFFECTS OF SULFHYDRYL-REAGENTS ON SAXITOXIN AND TETRODOTOXIN BLOCK OF VOLTAGE-DEPENDENT NA CHANNELS
DIFFERENTIAL-EFFECTS OF SULFHYDRYL-REAGENTS ON SAXITOXIN AND TETRODOTOXIN BLOCK OF VOLTAGE-DEPENDENT NA CHANNELS
复制标题
DOI：
10.1016/s0006-3495(94)80716-7
复制
发表时间：
1994-12-01
影响因子：
3.4
通讯作者：
HARTMANN, HA
中科院分区：
文献类型：
--
作者：
KIRSCH, GE;ALAM, M;HARTMANN, HA
我们探索了一种半胱氨酸残基，它可以抵抗河豚毒素(TTX)阻断心脏钠通道，与膜封闭的半胱氨酸特异性的甲硫磺酸盐(MTS)类似物。将带正电的基团共价加到半胱氨基上，使孔电导降低了87%。用河豚毒素(TTX)治疗可以选择性地阻止这种效果，但不能用萨曲霉毒素(STX)。加入一个带负电荷的基团选择性地抑制STX阻断，而不影响TTX阻断。这些结果与将暴露的半胱氨基硫基放置在TTX孔口附近的模型一致，但不支持STX和TTX可以互换的论点。这两种毒素之间的惊人差异与毒素-受体复合体在STX或TTX结合时可以呈现不同构象的假设一致。
We have probed a cysteine residue that confers resistance to tetrodotoxin (TTX) block in heart Na channels, with membrane-impermeant, cysteine-specific, methanethiosulfonate (MTS) analogs. Covalent addition of a positively charged group to the cysteinyl sulfhydryl reduced pore conductance by 87%. The effect was selectively prevented by treatment with TTX, but not saxitoxin (STX). Addition of a negatively charged group selectively inhibited STX block without affecting TTX block. These results agree with models that place an exposed cysteinyl sulfhydryl in the TTX site adjacent to the mouth of the pore, but do not support the contention that STX and TTX are interchangeable. The surprising differences between the two toxins are consistent with the hypothesis that the toxin-receptor complex can assume different conformations when STX or TTX bound.