Picomolar nitric oxide signals from central neurons recorded using ultrasensitive detector cells

Wood, K.C., Batchelor, A.M., Bartus, K., Harris, K.L., Garthwaite, G., Vernon, J. and Garthwaite, J. 2011. Picomolar nitric oxide signals from central neurons recorded using ultrasensitive detector cells. Journal of Biological Chemistry. 286 (50), pp. 43172-43181.

TitlePicomolar nitric oxide signals from central neurons recorded using ultrasensitive detector cells
AuthorsWood, K.C., Batchelor, A.M., Bartus, K., Harris, K.L., Garthwaite, G., Vernon, J. and Garthwaite, J.
Abstract

Nitric oxide (NO) is a widespread signaling molecule with potentially multifarious actions of relevance to health and disease. A fundamental determinant of how it acts is its concentration, but there remains a lack of coherent information on the patterns of NO release from its sources, such as neurons or endothelial cells, in either normal or pathological conditions. We have used detector cells having the highest recorded NO sensitivity to monitor NO release from brain tissue quantitatively and in real time. Stimulation of NMDA receptors, which are coupled to activation of neuronal NO synthase, routinely generated NO signals from neurons in cerebellar slices. The average computed peak NO concentrations varied across the anatomical layers of the cerebellum, from 12 to 130 pm. The mean value found in the hippocampus was 200 pm. Much variation in the amplitudes recorded by individual detector cells was observed, this being attributable to their location at variable distances from the NO sources. From fits to the data, the NO concentrations at the source surfaces were 120 pm to 1.4 nm, and the underlying rates of NO generation were 36–350 nm/s, depending on area. Our measurements are 4–5 orders of magnitude lower than reported by some electrode recordings in cerebellum or hippocampus. In return, they establish coherence between the NO concentrations able to elicit physiological responses in target cells through guanylyl cyclase-linked NO receptors, the concentrations that neuronal NO synthase is predicted to generate locally, and the concentrations that neurons actually produce.

JournalJournal of Biological Chemistry
Journal citation286 (50), pp. 43172-43181
ISSN0021-9258
YearOct 2011
PublisherAmerican Society for Biochemistry and Molecular Biology
Digital Object Identifier (DOI)doi:10.1074/jbc.M111.289777
Publication dates
PublishedOct 2011

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