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.
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J
J
Fjell
T R
TR
Cummins
K
K
Fried
J A
JA
Black
S G
SG
Waxman
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D016650:Fluorescein-5-isothiocyanate; D005727:Ganglia, Spinal / Q000378:metabolism*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D017136:Ion Transport; D037102:Lectins / Q000378:metabolism*; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000096:biosynthesis*
D001323:Autoantibodies; D037102:Lectins; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C568319:Scn10a protein, rat; D015222:Sodium Channels; D012964:Sodium; D016650:Fluorescein-5-isothiocyanate