Acquired channelopathies in nerve injury and MS.
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.
Waxman
S G
SG
Department of Neurology and the Paralyzed Veterans of America, Yale University School of Medicine, New Haven 06510, USA. stephen.waxman@yale.edu
D001369:Axons / Q000502:physiology; D006801:Humans; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology*; D009437:Neuralgia / Q000503:physiopathology*; D010292:Paresthesia / Q000503:physiopathology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000503:physiopathology; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels