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 GABA, 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 GABA, receptors were expressed. GABA-induced CI-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 GABA, receptor and the gamma(2s) subunit is involved in its action. (C) 1998 Rapid Science Ltd.