Regulation of Nav1.7 function. (360G-Wellcome-081112_Z_06_Z)
Gene knock-out studies have shown that the voltage-gated sodium channel Nav1.7 plays an essential role in inflammatory pain and noxious mechanosensation. Human heritable inflammatory pain conditions have also been mapped to gain-of-function mutations in Nav1.7. A range of inflammatory mediators (e.g. NGF, carrageenan, formalin) acting through different second messenger systems all require Nav1.7 to alter pain thresholds in the periphery by unknown mechanisms. We will investigate how inflammat ory mediators alter Nav1.7 activity and neuronal excitability in the hope of finding new routes to interfere with Nav1.7 function. To do this we will study epitope-tagged and fluorescent forms of a mutated (TTX-resistant) Nav1.7 expressed in native sensory neurons lacking other TTX-resistant channels. We will investigate the effects of inflammatory mediators on Nav1.7 function and expression using electrophysiological and trafficking assays. The major role of Nav1.7 in noxious mechanosensation suggests that Nav1.7 could be part of macro-molecular complex in nerve terminals that controls pain thresholds. We will identify proteins interacting with Nav1.7 using a yeast-2-hybrid screen employing an excellent DRG-derived yeast library and investigate the role of validated accessory proteins on Nav1.7 trafficking, and function as well as their possible contribution to mechanosensation.
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Grant Details
Amount Awarded | 370877 |
Applicant Surname | Wood |
Approval Committee | Molecular and Cellular Neuroscience Funding Committee |
Award Date | 2006-10-12T00:00:00+00:00 |
Financial Year | 2006/07 |
Grant Programme: Title | Project Grant |
Internal ID | 081112/Z/06/Z |
Lead Applicant | Prof John Wood |
Other Applicant(s) | Dr Mohammed Nassar |
Partnership Value | 370877 |
Planned Dates: End Date | 2009-12-03T00:00:00+00:00 |
Planned Dates: Start Date | 2006-12-04T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |