Dynamic and interacting profiles of ⋠NO and O2 in rat hippocampal slices

Nitric oxide (⋅NO) is a ubiquitous signaling molecule that participates in the neuromolecular phenomena associated with memory formation. In the hippocampus, neuronal ⋅NO production is coupled to the activation of the NMDA-type of glutamate receptor. Although ⋅NO-mediated signaling has been associated with soluble guanylate cyclase activation, cytochrome oxidase is also a target for this gaseous free radical, for which ⋅NO competes with O2. Here we show, for the first time in a model preserving tissue cytoarchitecture (rat hippocampal slices) and at a physiological O2 concentration, that endogenous NMDA-evoked ⋅NO production inhibits tissue O2 consumption for submicromolar concentrations. The simultaneous real-time recordings reveal a direct correlation between the profiles of ⋅NO and O2 in the CA1 subregion of the hippocampal slice. These results, obtained in a system close to in vivo models, strongly support the current paradigm for O2 and ⋅NO interplay in the regulation of cellular respiration.