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

Although classical neurophysiological doctrine rested on the concept of the sodium channel, it is now clear that there are nearly a dozen sodium chann el genes, each encoding a molecularly distinct channel. Different repertoir es of channels endow different types of neurons with distinct transduction and encoding properties. Sodium channel expression is highly dynamic, exhib iting plasticity at both the transcriptional and post-transcriptional level s. In some types of neurons within the normal nervous system, e.g, hypothal amic magnocellular neurosecretory neurons, changes in sodium channel gene e xpression occur in association with the transition from a quiescent to a bu rsting state; these changes are accompanied by the insertion of a different set of sodium channel subtypes in the cell membrane, a form of molecular p lasticity which results in altered electrogenic properties. Dysregulation o f sodium channel genes has been observed in a number of disease states. For example: transection of the peripheral axons of spinal sensory neurons tri ggers down-regulation of some sodium channel gents, and up-regulation of ot her sodium channel genes: the resultant changes in sodium channel expressio n contribute to hyperexcitability that can lead to chronic pain. There is a lso evidence, in experimental models of demyelination and in post-mortem ti ssue from patients with multiple sclerosis, for dysregulation of sodium cha nnel gene expression in the cell bodies of some neurons whose axons have be en demyelinated, suggesting that an acquired channelopathy may contribute t o the pathophysiology of demyelinating diseases such as multiple sclerosis. The dynamic nature of sodium channel gene expression makes it a complex to pic for investigation, but it also introduces therapeutic opportunities, si nce subtype-specific sodium channel modulating drugs may soon be available. (C) 2000 Elsevier Science B.V. All rights reserved.