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, 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.
Cohen-Armon
M
M
Department of Biochemistry, George S. Wise Institute of Life Sciences, Ramat Aviv, Israel.
Sokolovsky
M
M
Dascal
N
N
D000818:Animals; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology*; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D012333:RNA, Messenger; D015222:Sodium Channels; D013873:Thionucleotides; C034883:guanosine 5'-O-(2-thiotriphosphate); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005680:gamma-Aminobutyric Acid; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D007608:Kainic Acid