More MS news articles for Jan 2002

Diverse functions and dynamic expression of neuronal sodium channels

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11771649&dopt=Abstract

Novartis Found Symp 2002;241:34-51; discussion 51-60, 226-32
Waxman SG, Cummins TR, Black JA, Dib-Hajj S.
Department of Neurology and PVA/EPVA Neuroscience Research Center, Yale School of Medicine, New Haven, CT 06510, USA.

Nearly a dozen genes encode different Na channels, sharing a common overall motif but with subtly different amino acid sequences.

Physiological signatures have now been established for some Na+ channels and it is clear that, from a functional point of view, Na+ channels are not all the same: different channels can have different physiological characteristics, and they can play different roles in the physiology of excitable cells.

Moreover, the expression of Na+ channels within neurons is not a static process.

Plasticity of Na+ channel gene expression occurs in the normal nervous system, where it accompanies transitions between different physiological states (e.g. low-frequency versus high-frequency firing states) in some types of neurons.

Maladaptive changes in Na+ channel gene expression also occur in some pathological neurons.

For example, transection of the peripheral axons of spinal sensory neurons triggers downregulation of some Na+ channel genes and up-regulation of others, resulting in changes in Na+ current expression that produce hyperexcitability, thereby contributing to chronic pain.

There is also recent evidence for the expression of normally silent Na+ channel genes in Purkinje cells in experimental models of demyelinating diseases and in a human disease, multiple sclerosis; this dysregulation of Na+ channel expression may interfere with neuronal function in these disorders.

The diversity and dynamic nature of Na+ channel expression introduce a high degree of complexity into the nervous system and present challenges for neuroscientists.

In addition, they may present therapeutic opportunities as selective modulators for various Na+ channel subtypes become available.
 

PMID: 11771649 [PubMed - in process]