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.