Diverse functions and dynamic expression of neuronal sodium channels.
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.
Waxman
Stephen G
SG
Department of Neurology and PVA/EPVA Neuroscience Research Center, Yale School of Medicine, New Haven, CT 06510, USA.
Cummins
Theodore R
TR
Black
Joel A
JA
Dib-Hajj
Sulayman
S
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D009474:Neurons / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; D013779:Tetrodotoxin