Activation of a G protein promotes agonist responses to calcium channel ligands
Activation of a G protein promotes agonist responses to calcium channel ligands
复制标题
G 蛋白的激活促进对钙通道配体的激动剂反应
作者：
R. H. Scott;A. Dolphin
鸟苷酸结合（G）蛋白的激活是将某些受体与电压激活钙通道抑制偶联的重要步骤1 -3。我们先前已经观察到GTP类似物增强受体激动剂的作用并抑制培养的背根神经节（DRG）神经元中的钙电流2，4。钙通道电流的残余持续“L型”成分5对内部鸟苷5′-O-3-硫代三磷酸（GTP-γ-S）4的抑制具有抗性。由于钙通道拮抗剂如D 600、硝苯地平和地尔硫卓6，7抑制L电流5，8，9，我们检测了它们对GTP-γ-S修饰电流的影响。在存在内部GTP-γ-S的情况下，这些化合物均能迅速且非常显著地增强钙通道电流，并且这种作用可被百日咳毒素阻止，百日咳毒素可使G蛋白Gi/G 0发生ADP核糖基化（综述见参考文献10）。我们认为，这种增强表明，活化的G蛋白可以与钙通道相互作用，这增强了钙通道配体在其激动剂位点上的通道在其静息状态的行动11，12。这些结果代表了鸟嘌呤核苷酸能够影响细胞对钙通道配体的反应的第一个电生理证据。
The activation of a guanine nucleotide binding (G) protein is an essential step in coupling certain receptors to the inhibition of voltage-activated calcium channels1–3. We have previously observed that analogues of GTP potentiate the effect of receptor agonists and inhibit calcium currents in cultured dorsal root ganglion (DRG) neurones2,4. A residual sustained 'L-type' component5 of the calcium channel current is resistant to inhibition by internal guanosine 5′-O-3-thiotriphosphate (GTP-γ-S)4. Because calcium channel antagonists such as D600, nifedipine and diltiazem6,7 inhibit L currents5,8,9, we examined their effect on GTP-γ-S-modified currents. These compounds all produced a rapid and very marked potentiation of calcium channel currents in the presence of internal GTP-γ-S and this effect was prevented by pertussis toxin which ADP ribosylates the G proteins Gi/G0 (for review see ref. 10). We suggest that this potentiation indicates that activated G protein can interact with the calcium channel, and that this enhances the action of calcium channel ligands at their agonist sites on the channel in its resting state11,12. These results represent the first electrophysiological evidence that guanine nucleotides are able to influence cellular responses to calcium channel ligands.