Klein Joshua P, Tendi Elisabetta A, Dib-Hajj Sulayman D, Fields R Douglas, Waxman Stephen G
Department of Neurology and PVA/EPVA Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Neurosci Res. 2003 Oct 15;74(2):192-8. doi: 10.1002/jnr.10768.
Peripheral nerve injury induces changes in the level of gene expression for sodium channels Nav1.3, Nav1.8, and Nav1.9 within dorsal root ganglion (DRG) neurons, which may contribute to the development of hyperexcitability, ectopic neuronal discharge, and neuropathic pain. The mechanism of this change in sodium channel expression is unclear. Decreased availability of neurotrophic factors following axotomy contributes to these changes in gene transcription, but the question of whether changes in intrinsic neuronal activity levels alone can trigger changes in the expression of these sodium channels has not been addressed. We examined the effect of electrical stimulation on the expression of Nav1.3, Nav1.8, and Nav1.9 by using cultured embryonic mouse sensory neurons under conditions in which nerve growth factor (NGF) was not limiting. Expression of Nav1.3 was not significantly changed following stimulation. In contrast, we observed activity-dependent down-regulation of Nav1.8 and Nav1.9 mRNA and protein levels after stimulation, as demonstrated by quantitative polymerase chain reaction and immunocytochemistry. These results show that a change in neuronal activity can alter the expression of sodium channel genes in a subtype-specific manner, via a mechanism independent of NGF withdrawal.
外周神经损伤会导致背根神经节（DRG）神经元中钠通道Nav1.3、Nav1.8和Nav1.9的基因表达水平发生变化，这可能有助于兴奋性增高、异位神经元放电和神经性疼痛的发展。钠通道表达这种变化的机制尚不清楚。轴突切断后神经营养因子可用性的降低促成了这些基因转录的变化，但仅内在神经元活动水平的变化是否能触发这些钠通道表达的变化这一问题尚未得到解决。我们在神经生长因子（NGF）不存在限制的条件下，通过使用培养的胚胎小鼠感觉神经元，研究了电刺激对Nav1.3、Nav1.8和Nav1.9表达的影响。刺激后Nav1.3的表达没有显著变化。相比之下，通过定量聚合酶链反应和免疫细胞化学证明，我们观察到刺激后Nav1.8和Nav1.9的mRNA和蛋白质水平出现了活动依赖性下调。这些结果表明，神经元活动的变化可通过一种独立于NGF缺失的机制，以亚型特异性方式改变钠通道基因的表达。
