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

Songjiang Luo, Martine Jaegle, Roy Li, George R. Ehring, Dies Meijer, Simon R. Levinson

Research output: Contribution to journalArticlepeer-review

Abstract

Among sodium channel isoforms, Na(v)1.6 is selectively expressed at nodes of Ranvier in both the CNS and the PNS. However, non-Na(v)1.6 isoforms such as Na(v)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(SCE/geo), 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-Na(v)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 Na(v)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. J. Comp. Neurol. 522:4057-4073, 2014. (c) 2014 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)4057-4073
Number of pages17
JournalJournal of Comparative Neurology
Volume522
Issue number18
Early online date22 Jul 2014
DOIs
Publication statusPublished - 15 Dec 2014

Keywords

  • sodium channel
  • isoform
  • node of Ranvier
  • myelination
  • Oct6
  • DRG
  • NA+ CHANNELS
  • TRANSCRIPTION FACTOR
  • DEVELOPING CNS
  • SCHWANN-CELLS
  • EXPRESSION
  • OCT-6
  • NA(V)1.6
  • AXONS
  • IDENTIFICATION
  • REMYELINATION

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