title: Oligodendrocytes assist in the maintenance of sodium channel clusters independent of the myelin sheath.
abstract: To ensure rapid and efficient impulse conduction, myelinated axons establish and maintain specific protein domains. For instance, sodium (Na+) channels accumulate in the node of Ranvier; potassium (K+) channels aggregate in the juxtaparanode and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the mechanisms that control the initial clustering of these proteins is limited and less is known about domain maintenance. Correlative data indicate that myelin formation and/or mature myelin-forming cells mediate formation of all three domains. Here, we test whether myelin is required for maintaining Na+ channel domains in the nodal gap by employing two demyelinating murine models: (1) cuprizone ingestion, which induces complete demyelination through oligodendrocyte toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo spontaneous adult-onset demyelination without oligodendrocyte death. Our data indicate that the myelin sheath is essential for long-term maintenance of sodium channel domains; however, oligodendrocytes, independent of myelin, provide a partial protective influence on the maintenance of nodal Na+ channel clusters. Thus, we propose that multiple mechanisms regulate the maintenance of nodal protein organization. Finally, we present evidence that following the loss of Na+ channel clusters the chronological progression of expression and reclustering of Na+ channel isoforms during the course of CNS remyelination recapitulates development.
authors.affiliation: Anatomy and Neurobiology, Sanger Hall 11-073, 1101 E. Marshall Street, PO Box 980709, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA. jldupree@vcu.edu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Dupree
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Mason
authors.forename: Jill R
authors.initials: JR
authors.lastname: Marcus
authors.forename: Michael
authors.initials: M
authors.lastname: Stull
authors.forename: Rock
authors.initials: R
authors.lastname: Levinson
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Matsushima
authors.forename: Brian
authors.initials: B
authors.lastname: Popko