Voltage-gated sodium current is the primary inward current underlying excitability throughout CNS. Relocalization and changes in density of sodium channels at axon initial segments or nodes of Ranvier are related with some diseases, such as Multiple Sclerosis, a disease involving demyelination of axons. Clinical deficits are related to dysfunction of sodium channels in those axons. Mutations in sodium channel can also cause pediatric febrile seizures. Sodium channels have three subunits: the pore-forming alpha subunit and two auxiliary subunits, beta-1 (or beta-3) and beta-2. Some evidence has suggested that there could be a link between beta subunits and myelin, therefore clustering of sodium channels in nodes of Ranvier could be impacted by the beta subunits of sodium channels. My project is designed to use beta knockout mice to provide a clear-cut test of this hypothesis. Although evidence has also shown that beta subunits have an important role on sodium channel gating, all those experiments were done with the genes expressed in cell line or Xenopus oocytes. Thus, those beta knockout mice also offer a great chance to investigate the current hypothesis. We have also proposed to use gene rescue technique to confirm that the phenotypes of knockout mice are due to the deficiency of particular genes.
| Chen, Yuan; Yu, Frank H; Sharp, Elizabeth M et al. (2008) Functional properties and differential neuromodulation of Na(v)1.6 channels. Mol Cell Neurosci 38:607-15 |
| Chen, Yuan; Yu, Frank H; Surmeier, D James et al. (2006) Neuromodulation of Na+ channel slow inactivation via cAMP-dependent protein kinase and protein kinase C. Neuron 49:409-20 |
