Down-regulation of transcripts for Na channel alpha-SNS in spinal sensory neurons following axotomy.
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.
Dib-Hajj
S
S
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Black
J A
JA
Felts
P
P
Waxman
S G
SG
D000818:Animals; D003714:Denervation; D015536:Down-Regulation; D005260:Female; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D015222:Sodium Channels