Dysregulation of axonal sodium channel isoforms after adult-onset chronic demyelination

Matthew N. Rasband, Tetsushi Kagawa, Eunice W. Park, Kazuhiro Ikenaka, James Trimmer

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Demyelination results in conduction block through changes in passive cable properties of an axon and in the expression and localization of axonal ion channels. We show here that adult-onset chronic demyelination, such as occurs in demyelinating disorders and after nerve injury, alters the complement of axonal voltage-dependent Na+ (Nav) channel isoforms and their localization. As a model, we used heterozygous transgenic mice with two extra copies of the proteolipid protein gene (Pip/-). Retinal ganglion cell axons in these mice myelinate normally, with young Pip/- and wild-type mice expressing Nav1.2 at low levels, whereas Nav1.6 is clustered in high densities at nodes of Ranvier. At 7 months of age, however, Pip/- mice exhibit severe demyelination and oligodendrocyte cell death, leading to a profound reduction in Nav1.6 clusters, loss of the paranodal axoglial apparatus, and a marked increase in Nav1.2. We conclude that myelin is crucial not only for node of Ranvier formation, but also to actively maintain the proper localization and complement of distinct axonal Nav channel isoforms throughout life. The altered Nav channel isoform localization and complement induced by demyelination may contribute to the pathophysiology of demyelinating disorders and nerve injury.

Original languageEnglish (US)
Pages (from-to)465-470
Number of pages6
JournalJournal of Neuroscience Research
Issue number4
StatePublished - Aug 15 2003
Externally publishedYes


  • Demyelination
  • Myelin
  • Node of Ranvier
  • Oligodendrocyte
  • Sodium channels

ASJC Scopus subject areas

  • Neuroscience(all)


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