DOWN-REGULATION OF TRANSCRIPTS FOR NA CHANNEL ALPHA-SNS IN SPINAL SENSORY NEURONS FOLLOWING AXOTOMY

Spinal sensory (dorsal root ganglion; DRG) neurons display slowly inac tivating, tetrodotoxin-resistant (TTX-R), and rapidly inactivating, TT X-sensitive (TTX-S) Na currents. Attenuation of the TTX-R Na current a nd 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 transcript s encoding the alpha-SNS subunit, which is associated with a slowly in activating, TTX-R current when expressed in oocytes, are reduced signi ficantly 5 days following axotomy of DRG neurons, and continue to be e xpressed at reduced levels, even after 210 days. Steady-state levels o f alpha-III transcripts, which are present at low levels in control DR G neurons, show a pattern of transiently increased expression. In situ hybridization using alpha-SNS- and alpha-III-specific riboprobes show ed a decreased signal for alpha-SNS, and an increased signal for alpha -III, in both large and small DRG neurons following axotomy. Reduced l evels of alpha-SNS may explain the selective loss of slowly inactivati ng, TTX-R current. The abnormal electrophysiological properties of DRG neurons following axonal injury thus appear to reflect a switch in Na channel gene expression.