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J Neurophysiol 81: 803-810, 1999;
0022-3077/99 $5.00
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The Journal of Neurophysiology Vol. 81 No. 2 February 1999, pp. 803-810
Copyright ©1999 by the American Physiological Society

In Vivo NGF Deprivation Reduces SNS Expression and TTX-R Sodium Currents in IB4-Negative DRG Neurons

Jenny Fjell,1,2,3 Theodore R. Cummins,1,2 Kaj Fried,3 Joel A. Black,1,2 and Stephen G. Waxman1,2

 1Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510;  2Neuroscience Research Center, Veterans Administration Medical Center, West Haven, Connecticut 06516; and  3Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden

In vivo NGF deprivation reduces SNS expression and TTX-R sodium currents in IB4-negative DRG neurons. Recent evidence suggests that changes in sodium channel expression and localization may be involved in some pathological pain syndromes. SNS, a tetrodotoxin-resistant (TTX-R) sodium channel, is preferentially expressed in small dorsal root ganglion (DRG) neurons, many of which are nociceptive. TTX-R sodium currents and SNS mRNA expression have been shown to be modulated by nerve growth factor (NGF) in vitro and in vivo. To determine whether SNS expression and TTX-R currents in DRG neurons are affected by reduced levels of systemic NGF, we immunized adult rats with NGF, which causes thermal hypoalgesia in rats with high antibody titers to NGF. DRG neurons cultured from rats with high antibody titers to NGF, which do not bind the isolectin IB4 (IB4-) but do express TrkA, were studied with whole cell patch-clamp and in situ hybridization. Mean TTX-R sodium current density was decreased from 504 ± 77 pA/pF to 307 ± 61 pA/pF in control versus NGF-deprived neurons, respectively. In comparison, the mean TTX-sensitive sodium current density was not significantly different between control and NGF-deprived neurons. Quantification of SNS mRNA hybridization signal showed a significant decrease in the signal in NGF-deprived neurons compared with the control neurons. The data suggest that NGF has a major role in the maintenance of steady-state levels of TTX-R sodium currents and SNS mRNA in IB4- DRG neurons in adult rats in vivo.

0022-3077/99 $5.00 Copyright © 1999 The American Physiological Society



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