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Patterned electrical activity modulates sodium channel expression in sensory neurons.

Joshua P Klein, Elisabetta A Tendi, Sulayman D Dib-Hajj, R Douglas Fields, Stephen G Waxman

J. Neurosci. Res., 2003 Oct 15 , 74, 192-8

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.