Nitric oxide inhibits NMDA currents in a subpopulation of substantia gelatinosa neurons of the adult rat spinal cord.

In the present study, the actions of nitric oxide (NO) on NMDA mediated excitatory neurotransmission in substantia gelatinosa (SG) neurons of the adult rat spinal cord were investigated. Bath application of the NO donor sodium-nitroso-N-acetylpenicillamine (SNAP) reversibly inhibited NMDA receptor mediated excitatory postsynaptic currents evoked by electrical stimulation of the dorsal root. These effects of SNAP were prevented by pre-incubation with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy PTIO) or the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, and were mimicked by the membrane permeable cGMP analogue dibutyryl cGMP. Finally, these effects were shown to be mediated at a postsynaptic level using acutely applied exogenous NMDA. In conclusion, we demonstrate for the first time the inhibition of NMDA mediated excitatory neurotransmission by NO in spinal cord SG neurons, an action mediated at least in part via the activation of guanylate cyclase.