title: The sodium channel isoform transition at developing nodes of Ranvier in the peripheral nervous system: dependence on a Genetic program and myelination-induced cluster formation.
abstract: Among sodium channel isoforms, Nav 1.6 is selectively expressed at nodes of Ranvier in both the CNS and the PNS. However, non-Nav 1.6 isoforms such as Nav 1.2 are also present at the CNS nodes in early development but gradually diminish later. It has been proposed that myelination is part of a glia-neuron signaling mechanism that produces this change in nodal isoform expression. The present study used isoform-specific antibodies to demonstrate that, in the PNS, four other neuronal sodium channel isoforms were also clustered at nodes in early development but eventually disappeared during maturation. To study possible roles of myelination in such transitions, we investigated the nodal expression of selected isoforms in the sciatic nerve of the transgenic mouse Oct6(ΔSCE/βgeo) , whose PNS myelination is delayed in the first postnatal week but eventually resumes. We found that delayed myelination retarded the formation of nodal channel clusters and altered the expression-elimination patterns of sodium channel isoforms, resulting in significantly reduced expression levels of non-Nav 1.6 isoforms in such delayed nodes. However, delayed myelination did not significantly affect the gene expression, protein synthesis, or axonal trafficking of any isoform studied. Rather, we found evidence for a developmentally programmed increase in neuronal Nav 1.6 expression with constant or decreasing neuronal expression of other isoforms that were unaffected by delayed myelination. Thus our results suggest that, in the developmental isoform switch of the PNS, myelination does not play a signaling role as that proposed for the CNS but rather serves only to form nodal clusters from existing isoform pools.
authors.affiliation: Department of Comprehensive Dentistry, University of Texas Health Science Center, San Antonio, Texas, 78229.
authors.forename: Songjiang
authors.initials: S
authors.lastname: Luo
authors.forename: Martine
authors.initials: M
authors.lastname: Jaegle
authors.forename: Roy
authors.initials: R
authors.lastname: Li
authors.forename: George R
authors.initials: GR
authors.lastname: Ehring
authors.forename: Dies
authors.initials: D
authors.lastname: Meijer
authors.forename: Simon R
authors.initials: SR
authors.lastname: Levinson
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000254:growth & development / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008159:Lumbar Vertebrae; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000378:metabolism; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D050816:Octamer Transcription Factor-6 / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000254:growth & development* / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D020033:Protein Isoforms; D012333:RNA, Messenger; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D050816:Octamer Transcription Factor-6
keywords: DRG; Oct6; isoform; myelination; node of Ranvier; sodium channel