Gamma subunit dependent modulation by nitric oxide (NO) in recombinant GABAA receptor.
The effect of nitric oxide (NO) on GABA induced Cl- current of recombinant GABAA receptors was studied. Either alpha 1 beta 2 gamma 2s or alpha 1 beta 2 subunit mRNAs synthesized from cDNA of mouse brain were injected into Xenopus oocytes and functional GABAA receptors were expressed. GABA-induced Cl- current was measured with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the GABA-induced Cl- current in the alpha 1 beta 2 gamma 2s subunit receptor in a dose-dependent manner. In alpha 1,beta 2 subunit receptor, NOC-18 had no effects on GABA-induced currents at low concentrations but showed potentiation at high concentration. These effects were antagonized by the NO extinguisher, carboxy-PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly acts at the GABAA receptor and the gamma 2s subunit is involved in its action.
Fukami
S
S
Department of Anesthesiology, Osaka University Medical School, Japan.
Uchida
I
I
Mashimo
T
T
Takenoshita
M
M
Yoshiya
I
I
D000818:Animals; D066298:In Vitro Techniques; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000737:chemistry*; D011994:Recombinant Proteins / Q000494:pharmacology; D014981:Xenopus
C093285:NOC 18; D009603:Nitroso Compounds; D010446:Peptide Fragments; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D009569:Nitric Oxide