Acquired channelopathies in nerve injury and MS

Although neurophysiologic doctrine has traditionally referred to "the" volt age-gated sodium channel, it is now clear that there are at least nine gene s that encode molecularly and physiologically distinct sodium channels. Mut ations 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 channe lopathies. Two examples of acquired channelopathies are discussed in this a rticle. Recent research has established that peripheral nerve injury can pr ovoke an acquired channelopathy in spinal sensory neurons; axonal transecti on 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 cel ls. Emerging evidence also suggests that an acquired channelopathy, charact erized by abnormal expression of sensory neuron specific sodium channels th at can alter impulse trafficking within Purkinje cells, may contribute to t he pathophysiology of MS. Subtype-specific drugs that selectively modulate various types of channels probably will soon be developed. The acquired cha nnelopathies associated with nerve injury and MS may thus represent prototy pe disorders that present therapeutic opportunities.