Down-regulation of transcripts for Na channel α-SNS in spinal sensory neurons following axotomy
- S. Dib-Hajj*,†,
- J. A. Black*,†,
- P. Felts*,†,‡, and
- S. G. Waxman*,†,§
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 for 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.
Footnotes
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↵ ‡ Present address: Department of Neurology, United Medical and Dental School, Guy’s Campus, London SE1 9RT, England.
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↵ § To whom reprint requests should be addressed.
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Dominick P. Purpura, Albert Einstein College of Medicine, Bronx, NY
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Abbreviations: DRG, dorsal root ganglion; dpa, days post axotomy; ISH, in situ hybridization; RT-PCR, reverse transcriptase–polymerase chain reaction; REP, restriction enzyme polymorphism; TTX, tetrodotoxin; TTX-S and TTX-R, TTX-sensitive and -resistant.
- Copyright © 1996, The National Academy of Sciences of the USA
