DESCRIPTION (provided by applicant): The goal of this research project is to test the hypothesis that voltage gated sodium channel beta subunits are cell adhesion molecules in vivo, and are involved in the formation of nodes of Ranvier as well as the recruitment of other molecules involved in the nodal signaling complex. An alternative model system using Zebrafish is being generated in our laboratory. First, the sodium channel beta subunits in Zebrafish will be cloned and characterized using an in vitro system and electrophysiological techniques. Preliminary data show that Zebrafish have beta subunits orthologous to higher vertebrates as well as novel subunits not previously characterized. Next, "knock down" fish will be generated which will allow us to examine the role of beta subunits in vivo using antisense RNA techniques. Finally, a dominant negative beta1subunit will be used to test the ability of the beta1subunit to recruit ankyrin to the plasma membrane. Understanding the mechanism of node of Ranvier formation is important to elucidating the mechanisms of demyelinating disease. Demyelinating diseases are characterized by a loss of myelin and an impairment of action potential conduction as nodes of Ranvier are lost. Understanding nodal formation can contribute to clarifying the triggers for demyelinating disease as well as potential therapies.