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Brain Res. 2000 Dec 15;886(1-2):5-14.

Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states(1).

Author information

1
Department of Neurology and PVA/EPVA Neuroscience Research Center, Yale School of Medicine, 333 Cedar Street, 06510, New Haven, CT, USA. stephen.waxman@yale.edu

Abstract

Although classical neurophysiological doctrine rested on the concept of the sodium channel, it is now clear that there are nearly a dozen sodium channel genes, each encoding a molecularly distinct channel. Different repertoires of channels endow different types of neurons with distinct transduction and encoding properties. Sodium channel expression is highly dynamic, exhibiting plasticity at both the transcriptional and post-transcriptional levels. In some types of neurons within the normal nervous system, e.g. hypothalamic magnocellular neurosecretory neurons, changes in sodium channel gene expression occur in association with the transition from a quiescent to a bursting state; these changes are accompanied by the insertion of a different set of sodium channel subtypes in the cell membrane, a form of molecular plasticity which results in altered electrogenic properties. Dysregulation of sodium channel genes has been observed in a number of disease states. For example, transection of the peripheral axons of spinal sensory neurons triggers down-regulation of some sodium channel genes, and up-regulation of other sodium channel genes; the resultant changes in sodium channel expression contribute to hyperexcitability that can lead to chronic pain. There is also evidence, in experimental models of demyelination and in post-mortem tissue from patients with multiple sclerosis, for dysregulation of sodium channel gene expression in the cell bodies of some neurons whose axons have been demyelinated, suggesting that an acquired channelopathy may contribute to the pathophysiology of demyelinating diseases such as multiple sclerosis. The dynamic nature of sodium channel gene expression makes it a complex topic for investigation, but it also introduces therapeutic opportunities, since subtype-specific sodium channel modulating drugs may soon be available.

PMID:
11119683
[Indexed for MEDLINE]

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