The effects of agents known to affect G-proteins on voltage-dependent, tetrodoxin-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-γ-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-β-S, had no effect on INa. The responses to γ-aminobutyric acid and kainate in the same oocytes were also attenuated by GTP-γ-S. Pertussis toxin, which inactivates some G-proteins by catalyzing thier ADP-ribosylation, enhanced INa, but did not prevent the inhibition of INa by GTP-γ-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.
- Sodium channel
- Xenopus oocyte