Neurology 2001 Jun 26;56(12):1621-7
Waxman SG
Although neurophysiologic doctrine
has traditionally referred to "the" voltage-gated sodium channel, it is
now clear that there are at least nine genes that encode molecularly and
physiologically distinct sodium channels.
Mutations of sodium channel genes
provide a basis for genetic channelopathies.
Dysregulated expression of sodium
channels due to alterations in activity of nonmutated channel genes, on
the other hand, can produce acquired channelopathies.
Two examples of acquired channelopathies
are discussed in this article. Recent research has established that peripheral
nerve injury can provoke an acquired channelopathy in spinal sensory neurons;
axonal transection triggers the turning-off of some previously active sodium
channel genes and the turning-on of at least one previously silent sodium
channel gene, a set of molecular changes that can result in hyperexcitability
of these cells.
Emerging evidence also suggests that
an acquired channelopathy, characterized by abnormal expression of sensory
neuron specific sodium channels that can alter impulse trafficking within
Purkinje cells, may contribute to the pathophysiology of MS.
Subtype-specific drugs that selectively
modulate various types of channels probably will soon be developed.
The acquired channelopathies associated
with nerve injury and MS may thus represent prototype disorders that present
therapeutic opportunities.
Department of Neurology and the
Paralyzed Veterans of America, Yale University School of Medicine, New
Haven 06510, USA. stephen.waxman@yale.edu