Modulation of Cellular Respiration by Endogenously Produced Nitric Oxide in Rat Hippocampal Slices

Nitric oxide (^•NO) is an ubiquitous signaling molecule that participates in molecular processes associated with several neural phenomena ranging from memory formation to excitotoxicity. In the hippocampus, neuronal ^•NO production is coupled to the activation of NMDA type glutamate receptors. Cytochrome c oxidase has emerged as a novel target for ^•NO, which competes with O₂ for binding to this mitochondrial complex. This reaction establishes ^•NO as a regulator of cellular metabolism and, possibly, mitochondrial production of reactive oxygen species which participate in cellular signaling. A major gap in the understanding of ^•NO bioactivity, namely, in the hippocampus, has been the lack of knowledge of its concentration dynamics. Here, we present a detailed description of the simultaneous recording of ^•NO and O₂ concentration dynamics in rat hippocampal slices. Carbon fiber microelectrodes are fabricated and applied for real-time measurements of both gases in a system close to in vivo models. This approach allows for a better understanding of the current paradigm by which an intricate interplay between ^•NO and O₂ regulates cellular respiration.