Functional specialization of the axon initial segment by isoform-specific sodium channel targeting

Tatiana Boiko, Audra Van Wart, John H. CaldWell, S. Rock Levinson, James Trimmer, Gary Matthews

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

Abstract

Voltage-dependent sodium channels cluster at high density at axon initial segments, where propagating action potentials are thought to arise, and at nodes of Ranvier. Here, we show that the sodium channel Nav1.6 is precisely localized at initial segments of retinal ganglion cells (RGCs), whereas a different isoform, Nav1.2, is found in the neighboring unmyelinated axon. During development, initial segments first expressed Nav1.2, and Nav1.6 appeared later, approximately in parallel with the onset of repetitive RGC firing. In Shiverer mice, Nav1.6 localization at the initial segment was unaffected, although Nav1.6 expression was severely disrupted in the aberrantly myelinated optic nerve. Targeting or retention of Nav1.6 requires molecular interactions that normally occur only at initial segments and nodes of Ranvier. Expression at nodes but not initial segments exhibits an additional requirement for intact myelination. Because of their high density at the initial segment, Nav1.6 channels may be crucial in determining neuronal firing properties.

Original languageEnglish (US)
Pages (from-to)2306-2313
Number of pages8
JournalJournal of Neuroscience
Volume23
Issue number6
StatePublished - Mar 15 2003
Externally publishedYes

Keywords

  • Action potential initiation
  • Development
  • Initial segment
  • Optic nerve
  • Retina
  • Retinal ganglion cell
  • Sodium channels

ASJC Scopus subject areas

  • Neuroscience(all)

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