title: Sodium channels as molecular targets in multiple sclerosis.
abstract: Sodium channels are expressed at high density in myelinated axons and play an obligatory role in conducting action potentials along axons within the mammalian brain and spinal cord. It is not surprising, therefore, that they are involved in several aspects of the pathophysiology of multiple sclerosis (MS). First, the deployment of additional sodium channels to demyelinated parts of the axon (which had expressed low densities of sodium channels when covered by the myelin) provides a molecular substrate for the restoration of action potential conduction, a process that contributes to remissions in patients with MS. Second, there is evidence for changes in the expression pattern of sodium channels within Purkinje cells, both in animal models of MS and in human MS. It has been hypothesized that dysregulated sodium channel expression may contribute to symptom production in MS. If this hypothesis is correct, subtype-specific channel blockade may be therapeutically effective as a symptomatic treatment for ataxia and other cerebellar symptoms in MS. Finally, a noninactivating sodium conductance can trigger calcium-mediated axonal injury via reverse sodium-calcium exchange. Identifying the underlying channel may permit the development of therapeutic strategies that will prevent or retard axonal degeneration in MS.
authors.affiliation: Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Center for Neuroscience Research, Yale University School of Medicine, New Haven, CT 06510, USA. stephen.waxman@yale.edu
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000200:Action Potentials; D001369:Axons; D003711:Demyelinating Diseases / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D012106:Research; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D015222:Sodium Channels