GAMMA-SUBUNIT DEPENDENT MODULATION BY NITRIC-OXIDE (NO) IN RECOMBINANT GABA(A) RECEPTOR

THE effect of nitric oxide (NO) on GABA induced Cl- current of recombi nant GABA, receptors was studied. Either alpha(1) beta(2) gamma(2s) Or alpha(1) beta(2) subunit mRNAs synthesized from cDNA of mouse brain w ere 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 d ose-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 Scienc e Ltd.