Nitric oxide signalling in the CNS. (360G-Wellcome-081512_Z_06_A)
Nitric oxide (NO) serves as a diffusible signalling molecule throughout the CNS. Despite progress, there remains a poor level of understanding about how this atypical messenger functions and this is the focus of the research proposal. To address the lack of knowledge of physiological or pathological NO signals (e.g. their amplitude, duration and spread) we have designed novel NO biosensors capable of registering physiological NO concentrations (predicted to be subnanomolar) and propose to use them to record NO formation from all the relevant sources in the CNS, namely from neuronal, endothelial and inducible NO synthases. The second aim is to analyze NO signal transduction through its guanylyl cyclase-coupled receptors in a quantitative manner. To do so, we have designed a new technique capable of recording receptor function in real time. Together, these first two components offer the hope of generating a quantitative description of NO signalling comparable to that existing for the major neurotransmitters. The third goal relates to NOcGMP signal transduction in the brain. Building on recent unexpected findings, the hypothesis under investigation is that endogenous NO acts on neurones to regulate (through cGMP) hyperpolarization-activated, cyclic nucleotide-gated ion channels.
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Grant Details
Amount Awarded | 63088 |
Applicant Surname | Garthwaite |
Approval Committee | Neurosciences And Mental Health |
Award Date | 2009-09-22T00:00:00+00:00 |
Financial Year | 2008/09 |
Grant Programme: Title | Programme Grant |
Internal ID | 081512/Z/06/A |
Lead Applicant | Prof John Garthwaite |
Partnership Value | 63088 |
Planned Dates: End Date | 2012-05-31T00:00:00+00:00 |
Planned Dates: Start Date | 2009-11-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |