Cohen-Armon M, Sokolovsky M, Dascal N
Department of Biochemistry, George S. Wise Institute of Life Sciences, Ramat Aviv, Israel.
Brain Res. 1989 Sep 4;496(1-2):197-203. doi: 10.1016/0006-8993(89)91066-4.
The effects of agents known to affect G-proteins on voltage-dependent, tetrodotoxin-sensitive Na+ channels were studied in Xenopus oocytes injected with rat brain RNA, using two-electrode voltage-clamp technique. The non-hydrolysable analogue of GTP, GTP-gamma-S, known to activate G-proteins, inhibited the Na+ current (INa). The decrease in the amplitude of INa was not accompanied by changes in activation or inactivation characteristics of the channel. The non-hydrolysable analogue of GDP, GDP-beta-S, had no effect on INa. The responses to gamma-aminobutyric acid and kainate in the same oocytes were also attenuated by GTP-gamma-S. Pertussis toxin, which inactivates some G-proteins by catalyzing their ADP-ribosylation, enhanced INa, but did not prevent the inhibition of INa by GTP-gamma-S. We conclude that the Na+ channel, and possibly the GABA and kainate receptors and/or channels, are coupled to a G-protein. The activation of the G-protein modulates the channels either directly, or via activation of biochemical cascade possibly involving production of second messengers and channel phosphorylation.
利用双电极电压钳技术，在注射了大鼠脑RNA的非洲爪蟾卵母细胞中研究了已知影响G蛋白的试剂对电压依赖性、河豚毒素敏感的Na⁺通道的作用。已知可激活G蛋白的GTP非水解类似物GTP-γ-S抑制了Na⁺电流（INa）。INa幅度的降低并未伴随着通道激活或失活特性的改变。GDP的非水解类似物GDP-β-S对INa无影响。在相同的卵母细胞中，GTP-γ-S也减弱了对γ-氨基丁酸和红藻氨酸的反应。百日咳毒素通过催化一些G蛋白的ADP核糖基化使其失活，增强了INa，但并未阻止GTP-γ-S对INa的抑制作用。我们得出结论，Na⁺通道，可能还有GABA和红藻氨酸受体和/或通道，与一种G蛋白偶联。G蛋白的激活要么直接调节通道，要么通过激活可能涉及第二信使产生和通道磷酸化的生化级联反应来调节通道。
