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


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 alpha-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 alpha-III transcripts, which are present at low levels in control DRG neurons, show a pattern of transiently increased expression. In situ hybridization using alpha-SNS- and alpha-III-specific riboprobes showed a decreased signal for alpha-SNS, and an increased signal for alpha-III, in both large and small DRG neurons following axotomy. Reduced levels of alpha-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.

SUBMITTER: Dib-Hajj S 

PROVIDER: S-EPMC26243 | biostudies-literature | 1996 Dec

REPOSITORIES: biostudies-literature

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

Dib-Hajj S S   Black J A JA   Felts P P   Waxman S G SG  

Proceedings of the National Academy of Sciences of the United States of America 19961201 25


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 alpha-SNS subunit, which is associated with a slowly inactivating  ...[more]

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