• Sheng Wang, Julian F R Paton, and Sergey Kasparov.
• Department of Physiology, School of Medical Sciences, Bristol Heart Institute, University of Bristol, Bristol, BS8 1TD, UK.
• Exp. Physiol. 2007 Mar 1; 92 (2): 371-82.

AbstractThe nucleus tractus solitarii (NTS) is a key central link in control of multiple homeostatic reflexes. A number of studies have demonstrated that exogenous and endogenous nitric oxide (NO) within NTS regulates visceral function, but further understanding of the role of NO in the NTS is hampered by the lack of information about its intracellular actions. We studied effects of NO in acute rat brainstem slices. Aqueous NO solution (NO(aq)) potentiated electrically evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively) in different neuronal subpopulations and, in some neurones, caused a depolarization. Similar effects were observed using the NO donor diethylamine NONOate (DEA/NO). The threshold NO concentration as determined using an NO electrochemical sensor was estimated as approximately 0.4 nm (EC(50) approximately 0.9 nm) for potentiating glutamatergic EPSPs but approximately 3 nm for monosynaptic GABAergic IPSPs. Bath application of the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) abolished NO(aq)- and DEA/NO-induced potentiation of evoked EPSPs, IPSPs and depolarization. All NO actions were mimicked by the non-NO-dependent guanylate cyclase activator Bay 41-2272. The effects of NO on EPSPs and IPSPs persisted in cells where postsynaptic sGC was blocked by ODQ and therefore were presynaptic, owing to a direct modulation of transmitter release combined with depolarization of presynaptic neurones. Therefore, while lower concentrations of NO may be important for fine tuning of glutamatergic transmission, higher concentrations are required to directly engage GABAergic inhibition. This differential sensitivity of excitatory and inhibitory connections to NO may be important for determining the specificity of the effects of this freely diffusible gaseous messenger.

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