Nitric oxide and excitatory postsynaptic currents in immature rat sympathetic preganglionic neurons in vitro

Neuronal nitric oxide synthase immunoreactivity was localized to sympathetic preganglionic neurons of the intermediolateral cell column and cyclic GMP immunoreactivity to nerve fibers projecting into the intermediolateral cell column of 20-25-day-old rats. Whole-cell patch-clamp recordings were made from sympathetic preganglionic neurons in spinal cord slices of immature rats and the role of nitric oxide and cyclic GMP on excitatory postsynaptic currents was studied. Superfusing the slices with the nitric oxide precursor L-arginine (300 microM) increased the amplitude of evoked excitatory postsynaptic currents as well as the frequency of spontaneous miniature excitatory postsynaptic currents in some neurons from minutes to over 1 h. The nitric oxide synthase inhibitor N(W)-nitro-L-arginine (100 microM) and the nitric oxide scavenger hemoglobin (100 microM) antagonized the potentiating effect of L-arginine. The nitric oxide donor sodium nitroprusside (100 microM) potentiated the synaptic currents in a manner similar to that of L-arginine and this effect was blocked by hemoglobin. The membrane-permeable cyclic GMP analogue dibutyryl guanosine 3',5'-cyclic monophosphate (350 microM), in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (750 microM), potentiated the evoked excitatory postsynaptic currents and increased the frequency of miniature excitatory postsynaptic currents; these effects were not prevented by hemoglobin. The results indicate that nitric oxide may facilitate the release of excitatory transmitters, possibly through a presynaptic cyclic GMP-dependent mechanism.