Modulation of the voltage-dependent sodium channel by agents affecting G-proteins: a study in Xenopus oocytes injected with brain RNA

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 (I_Na). The decrease in the amplitude of I_Na 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 I_Na. 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 I_Na, but did not prevent the inhibition of I_Na 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.