Cohen-Armon M, Sokolovsky M
J Biol Chem. 1986 Sep 25;261(27):12498-505.
The effects of the voltage-sensitive sodium channel activator batrachotoxin (BTX) on the binding properties of muscarinic receptors were studied in homogenates of rat atria. Also studied were the effects of muscarinic ligands on the binding of tritium-labeled batrachotoxin ([3H]BTX) to the same preparation. BTX (1 microM), which induces an open state in sodium channels, enhanced the affinity of binding of several agonists to the muscarinic receptors. Analysis of the data indicated that the effect of BTX was to increase the affinity of the agonists toward the high-affinity sites. Binding of antagonists was not affected by BTX. At higher concentrations of toxin, the density of the high affinity muscarinic sites was also affected. The binding of agonists (but not of antagonists) to muscarinic receptors in turn enhanced the specific binding of [3H]BTX to sodium channels. These effects on the muscarinic receptors and on the sodium channels were inhibited in the presence of Gpp(NH)p at concentrations lower than those bringing about conversion of binding sites from the high affinity to the low affinity conformation. On the basis of these findings we suggest that the opening of sodium channels and the binding of agonists to muscarinic receptors in rat atrial membranes are coupled events which are mediated by guanine nucleotide-binding protein(s). Such a hypothesis is consistent with previously proposed models for signal transduction in the membrane.
在大鼠心房匀浆中研究了电压敏感性钠通道激活剂蛙毒素（BTX）对毒蕈碱受体结合特性的影响。还研究了毒蕈碱配体对氚标记蛙毒素（[3H]BTX）与同一制剂结合的影响。能使钠通道处于开放状态的1微摩尔BTX增强了几种激动剂与毒蕈碱受体的结合亲和力。数据分析表明，BTX的作用是增加激动剂对高亲和力位点的亲和力。拮抗剂的结合不受BTX影响。在较高毒素浓度下，高亲和力毒蕈碱位点的密度也受到影响。激动剂（而非拮抗剂）与毒蕈碱受体的结合反过来增强了[3H]BTX与钠通道的特异性结合。在存在Gpp(NH)p的情况下，当浓度低于使结合位点从高亲和力构象转变为低亲和力构象的浓度时，对毒蕈碱受体和钠通道的这些作用受到抑制。基于这些发现，我们认为大鼠心房膜中钠通道的开放和激动剂与毒蕈碱受体的结合是由鸟嘌呤核苷酸结合蛋白介导的偶联事件。这样的假设与先前提出的膜信号转导模型一致。
