title: Structure-function studies on the voltage-gated sodium channel.
abstract: Recent research on structure-function relationships aspects of voltage-gated sodium channels (VGSCs) are reviewed. Data issued from the literature are summarized and compared, including results from our own studies. The latter deal with the effects of drug binding, deglycosylation and the role of hydrophobic residues in the voltage sensors. Methods mainly consist of circular dichroism (CD) to asses the channel's secondary structure and conductance measurements after reconstitution into planar lipid bilayers. Molecular modelling was also used to tentatively explain experimental data. Since 30% of the channel's mass are glycoconjugates, the effects of removing them were first investigated. Then, the effects of the neurotoxin Batrachotoxin and the anticonvulsant Lamotrigine were studied. Both drugs induced a significant increase in the channel's helical content and a molecular model shows that lamotrigine interacts with residues previously identified as forming the binding sites in the pore. Finally, the role of hydrophobic residues with long sidechains in the voltage sensors (S4s) was investigated. Recent research on related studies on VGSCs are discussed.
authors.affiliation: Institut de Biologie et Physiologie Cellulaires, UMR 6187 CNRS-Université de Poitiers, Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86022 POITIERS, France. Herve.Duclohier@univ-poitiers.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Duclohier
mesh_terms: D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D015222:Sodium Channels / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D015222:Sodium Channels