Sodium channel expression in NGF-overexpressing transgenic mice

Jenny Fjell, Theodore R. Cummins, Brian M. Davis, Kathryn M. Albers, Kaj Fried, Stephen G. Waxman, Joel A. Black

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Dorsal root ganglion (DRG) neurons depend on nerve growth factor (NGF) for survival during development, and for the maintenance of phenotypic expression of neuropeptides in the adult. NGF also plays a role in the regulation of expression of functional sodium channels in both PC12 cells and DRG neurons. Transgenic mice that overexpress NGF under the keratin promoter (hyper-NGF mice) show increased levels of NGF in the skin from embryonic day 11 through adulthood, hypertrophy of the peripheral nervous system and mechanical hyperalgesia. We show here that mRNA levels for specific sodium channel isotypes are greater in small (<30 μm diameter) DRG neurons from hyper-NGF mice compared to wild-type mice. Hybridization signals for sodium channel subunits αII and β2 displayed the most substantial enhancement in hyper-NGF mice, compared to wild-type mice DRG, and mRNA levels for αI, NaG, Na6, SNS/PN3, NaN, and β1 were also greater in hyper-NGF DRG. In contrast, the levels of αII and PN1 mRNAs were similar in neurons from hyper-NGF and wild-type DRG. Whole-cell patch-clamp studies showed no significant differences in the peak sodium current densities in hyper-NGF vs, wild-type DRG neurons. These data demonstrate that DRG neurons in wild-type mice have a heterogeneous pattern of sodium channel expression, which is similar to that previously described in rat, and suggest that transcripts of some, but not all, sodium channel mRNAs can be modulated by long-term overexpression of NGF.

Original languageEnglish (US)
Pages (from-to)39-47
Number of pages9
JournalJournal of Neuroscience Research
Volume57
Issue number1
DOIs
StatePublished - Jul 1 1999
Externally publishedYes

Keywords

  • Na6
  • NaG
  • NaN
  • Nerve growth factor
  • PN1
  • SNS/PN3
  • Sensory neurons
  • Sodium channels
  • Sodium currents

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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