Fjell J, Cummins T R, Fried K, Black J A, Waxman S G
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Neurophysiol. 1999 Feb;81(2):803-10. doi: 10.1152/jn.1999.81.2.803.
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.
最近的证据表明，钠通道表达和定位的变化可能与某些病理性疼痛综合征有关。SNS是一种对河豚毒素耐受（TTX-R）的钠通道，优先表达于小的背根神经节（DRG）神经元中，其中许多是伤害性感受神经元。在体外和体内，TTX-R钠电流和SNS mRNA表达已被证明受神经生长因子（NGF）调节。为了确定DRG神经元中SNS表达和TTX-R电流是否受全身NGF水平降低的影响，我们用NGF免疫成年大鼠，这会在对NGF抗体滴度高的大鼠中引起热痛觉减退。用全细胞膜片钳和原位杂交技术研究了从对NGF抗体滴度高的大鼠培养的DRG神经元，这些神经元不结合异凝集素IB4（IB4(-)）但表达TrkA。对照神经元和NGF缺乏神经元的平均TTX-R钠电流密度分别从504±77 pA/pF降至307±61 pA/pF。相比之下，对照神经元和NGF缺乏神经元之间的平均TTX敏感钠电流密度没有显著差异。SNS mRNA杂交信号的定量分析显示，与对照神经元相比，NGF缺乏神经元中的信号显著降低。数据表明，NGF在成年大鼠体内IB4(-) DRG神经元中TTX-R钠电流和SNS mRNA稳态水平的维持中起主要作用。
