Nitric oxide via cGMP-dependent mechanisms increases dye coupling and excitability of rat supraoptic nucleus neurons

Unlike many neuron populations, supraoptic nucleus (SON) neurons are rich i n both nitric oxide synthase (NOS) and the NO receptor-soluble guanylyl cyc lase (GC), the activation of which leads to cGMP accumulation. Elevations i n cGMP result in increased coupling among SON neurons. We investigated the effect of NO on dye coupling in SONs from male, proestrus virgin female, an d lactating rats. In 167 slices 263 SON neurons were recorded; 210 of these neurons were injected intracellulary tone neuron per SON) with Lucifer yel low (LY). The typically minimal coupling seen in virgin females was increas ed nearly fourfold by the NO precursor, L-arginine, or the NO donor, sodium niiroprusside (SNP). L-Arginine-induced coupling was abolished by a NOS in hibitor. In slices from male and lactating rats who have a higher basal inc idence of coupling, SNP increased coupling by approximately twofold over co ntrol (p < 0.03). SNP effects were prevented by the NO scavenger hemoglobin (20 mu M) and by the selective blocker of NO-activated GC, ODQ (10 mu M). These results suggest that NO released from cells within the SON can expand the coupled network of neurons and that this action occurs via cGMP-depend ent processes. Because increased coupling is associated with elevated SON n euronal excitability, we also studied the effects of 8-bromo-cGMP on excita bility. In both phasically and continuously firing neurons 8-bromo-cGMP (1- 2 mM), but not cGMP, produced membrane depolarizations accompanied by membr ane conductance increases, Conductance increases remained when depolarizati ons were eliminated by current-clamping the membrane potential. Thus, NO-in duced cGMP increases SON neuronal coupling and excitability.