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The Journal of Neuroscience, June 1, 1999, 19(11):4270-4279
Nitric Oxide via cGMP-Dependent Mechanisms Increases Dye Coupling and Excitability of Rat Supraoptic Nucleus Neurons
Qin Z. Yang and Glenn I. Hatton Department of Neuroscience, University of California, Riverside, California 92521
Unlike many neuron populations, supraoptic nucleus (SON) neurons are rich in both nitric oxide synthase (NOS) and the NO receptor-soluble guanylyl cyclase (GC), the activation of which leads to cGMP accumulation. Elevations in cGMP result in increased coupling among SON neurons. We investigated the effect of NO on dye coupling in SONs from male, proestrus virgin female, and lactating rats. In 167 slices 263 SON neurons were recorded; 210 of these neurons were injected intracellularly (one neuron per SON) with Lucifer yellow (LY). The typically minimal coupling seen in virgin females was increased nearly fourfold by the NO precursor, L-arginine, or the NO donor, sodium nitroprusside (SNP). L-Arginine-induced coupling was abolished by a NOS inhibitor. In slices from male and lactating rats who have a higher basal incidence of coupling, SNP increased coupling by approximately twofold over control (p < 0.03). SNP effects were prevented by the NO scavenger hemoglobin (20 µM) and by the selective blocker of NO-activated GC, ODQ (10 µM). 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-dependent processes. Because increased coupling is associated with elevated SON neuronal excitability, we also studied the effects of 8-bromo-cGMP on excitability. In both phasically and continuously firing neurons 8-bromo-cGMP (1-2 mM), but not cGMP, produced membrane depolarizations accompanied by membrane conductance increases. Conductance increases remained when depolarizations were eliminated by current-clamping the membrane potential. Thus, NO-induced cGMP increases SON neuronal coupling and excitability.
Key words: gap junctions; guanylyl cyclase inhibition; hemoglobin; L-NAME; ODQ; sodium nitroprusside; 8-bromo-cGMP
Copyright © 1999 Society for Neuroscience 0270-6474/99/19114270-10$05.00/0
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