MODULATION BY NITRIC-OXIDE OF RAT-BRAIN GABA(A) RECEPTORS

The effect of nitric oxide (NO) on the function of GABA(A) receptors was studied in two different rat brain neuron populations. Cerebral cortex neuronal GABA(A) receptors were studied by preparing microsacs and evaluating Cl-36(-) accumulation. Whether nitric oxide was provided by sodium nitroprusside (SNP) or by the metabolic precursor arginine there was a 15-25% reduction in the V-max for GABA-stimulated Cl-36(-) accumulation. The arginine effect could be reversed by the NO synthase (NOS) inhibitor N(o)mega-nitro-L-arginine. GABA(A) receptor mediated Cl- currents were studied in rat cerebellar granule cells by whole-cell patch clamp. S-Nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside and L-arginine reduced the Cl- current elicited by 10 mu M GABA. The L-arginine effect was reversible upon its washing out. This circumstance indicates that NO produced by endogenous NOS can inhibit GABA(A) receptor function in cerebellar granule cells.