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Titolo:
Upregulation of a silent sodium channel after peripheral, but not central,nerve injury in DRG neurons
Autore:
Black, JA; Cummins, TR; Plumpton, C; Chen, YH; Hormuzdiar, W; Clare, JJ; Waxman, SG;
Indirizzi:
Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA Yale Univ New Haven CT USA 06510 ed, Dept Neurol, New Haven, CT 06510 USA Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 ed, Dept Neurol, New Haven, CT 06520 USA Yale Univ, Sch Med, Paralyzed Vet Amer Eastern Paralyzed Vet Assoc, Neurosci Res Ctr, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 eurosci Res Ctr, New Haven, CT 06520 USA Vet Affairs Connecticut, Rehabil Res Ctr, W Haven, CT 06516 USA Vet Affairs Connecticut W Haven CT USA 06516 s Ctr, W Haven, CT 06516 USA Glaxo Wellcome Res & Dev Ltd, Med Res Ctr, Mol Pharmacol Unit, Stevenage SG1 2NY, Herts, England Glaxo Wellcome Res & Dev Ltd Stevenage Herts England SG1 2NY rts, England
Titolo Testata:
JOURNAL OF NEUROPHYSIOLOGY
fascicolo: 5, volume: 82, anno: 1999,
pagine: 2776 - 2785
SICI:
0022-3077(199911)82:5<2776:UOASSC>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPINAL SENSORY NEURONS; ROOT GANGLION NEURONS; SUBUNIT MESSENGER-RNAS; ELECTROPHYSIOLOGICAL CHARACTERISTICS; ONGOING ACTIVITY; DOWN-REGULATION; RAT-BRAIN; ALPHA-SNS; AXOTOMY; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Waxman, SG Yale Univ, Sch Med, Dept Neurol, LCI 707,POB 208018, New Haven,CT 06510 USA Yale Univ LCI 707,POB 208018 New Haven CT USA 06510 T 06510 USA
Citazione:
J.A. Black et al., "Upregulation of a silent sodium channel after peripheral, but not central,nerve injury in DRG neurons", J NEUROPHYS, 82(5), 1999, pp. 2776-2785

Abstract

After transection of their axons within the sciatic nerve, DRG neurons become hyperexcitable. Recent studies have demonstrated the emergence of a rapidly repriming tetrodotoxin (TTX)-sensitive sodium current that may accountfor this hyperexcitability in axotomized small (<27 mu m diam) DRG neurons, but its molecular basis has remained unexplained. It has been shown previously that sciatic nerve transection leads to an upregulation of sodium channel III transcripts, which normally are present at very low levels in DRG neurons, in adult rats. We show here that TTX-sensitive currents in small DRG neurons, after transection of their peripheral axonal projections, reprime more rapidly than those in control neurons throughout a voltage range of-140 to -60 mV, a finding that suggests that these currents are produced by a different sodium channel. After transection of the central axonal projections (dorsal rhizotomy) of these small DRG neurons, in contrast, the repriming kinetics of TTX-sensitive sodium currents remain similar to those of control (uninjured) neurons. We also demonstrate, with two distinct antibodies directed against different regions of the type III sodium channel, thatsmall DRG neurons display increased brain type III immunostaining when studied 7-12 days after transection of their peripheral, but not central, projections. Type III sodium channel immunoreactivity is present within somata and neurites of peripherally axotomized, but not centrally axotomized, neurons studied after <24 h in vitro. Peripherally axotomized DRG neurons in situ also exhibit enhanced type III staining compared with control neurons, including an accumulation of type III sodium channels in the distal portion of the ligated and transected sciatic nerve, but these changes are not seenin centrally axotomized neurons. These observations are consistent with a contribution of type III sodium channels to the rapidly repriming sodium currents observed in peripherally axotomized DRG neurons and suggest that type III channels may at least partially account for the hyperexcitibility of these neurons after injury.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 17:43:38