Down-regulation of transcripts for Na channel α-SNS in spinal sensory neurons following axotomy

S. Dib-Hajj, J. A. Black, P. Felts, S. G. Waxman

Research output: Contribution to journalArticlepeer-review

214 Citations (Scopus)

Abstract

Spinal sensory (dorsal root ganglion; DRG) neurons display slowly inactivating, tetrodotoxin-resistant (TTX-R), and rapidly inactivating, TTX- sensitive (TTX-S) Na currents. Attenuation of the TTX-R Na current and enhancement of TTX-S Na current have been demonstrated in cutaneous afferent DRG neurons in the adult rat after axotomy and may underlie abnormal bursting. We show here that steady-state levels of transcripts encoding the α-SNS subunit, which is associated with a slowly inactivating, TTX-R current when expressed in oocytes, are reduced significantly 5 days following axotomy of DRG neurons, and continue to be expressed at reduced levels, even after 210 days. Steady-state levels of α-III transcripts, which are present at low levels in control DRG neurons, show a pattern of transiently increased expression. In situ hybridization using α-SNS- and α-III-specific riboprobes showed a decreased signal for α-SNS, and an increased signal fur α-III, in both large and small DRG neurons following axotomy. Reduced levels of α-SNS may explain the selective loss of slowly inactivating, TTX-R current. The abnormal electrophysiological properties of DRG neurons following axonal injury thus appear to reflect a switch in Na channel gene expression.

Original languageEnglish
Pages (from-to)14950-14954
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number25
DOIs
Publication statusPublished - 10 Dec 1996

Keywords

  • axonal injury
  • pain

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