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

TY - JOUR

T1 - Down-regulation of transcripts for Na channel α-SNS in spinal sensory neurons following axotomy

AU - Dib-Hajj, S.

AU - Black, J. A.

AU - Felts, P.

AU - Waxman, S. G.

PY - 1996/12/10

Y1 - 1996/12/10

N2 - 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.

AB - 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.

KW - axonal injury

KW - pain

UR - https://www.scopus.com/pages/publications/0029907091

U2 - 10.1073/pnas.93.25.14950

DO - 10.1073/pnas.93.25.14950

M3 - Article

C2 - 8962162

AN - SCOPUS:0029907091

SN - 0027-8424

VL - 93

SP - 14950

EP - 14954

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 25

ER -