saxitoxin and Multiple-Sclerosis

Multiple Sclerosis is a chronic demyelinating disease of the central nervous system of undetermined etiology. Damage of myelinated fibers leads to block of conduction of impulses. In myelinated axons sodium channels are expressed at high density and they play a very important role in the conduction of nervous impulse. In myelinated fibers affected by Multiple Sclerosis substantial variations of sodium channels pattern occurs. These variations can help to explain pathophysiological and clinical aspects of Multiple Sclerosis and open a new way to approach and, probably, treat this disease.

Topics: Humans; Multiple Sclerosis; Nerve Fibers, Myelinated; Saxitoxin; Sodium Channels

Redistribution of sodium channels along demyelinated pathways in multiple sclerosis (MS) could be an important event in restoring conduction prior to other reparative mechanisms such as remyelination. Sodium channels in human multiple sclerosis lesions were identified by quantitative light microscopic autoradiography using tritiated saxitoxin (STX), a highly specific sodium channel ligand. Demyelinated areas in various central nervous system regions containing denuded but vital axons exhibited a high increase of STX-binding sites by up to a factor of 4 as compared to normal human white matter. This important finding could explain aspects of fast clinical remissions and 'silent' MS lesions on functional and morphological properties. Demyelinated axons may functionally reorganize their membranes and adapt properties similar to those of slow conducting unmyelinated nerve fibres which have a higher amount and a more diffuse distribution of STX binding sites. This report is the first description of an altered distribution of voltage-sensitive sodium channels in human multiple sclerosis lesions.

Topics: Aged; Autoradiography; Axons; Binding Sites; Central Nervous System; Humans; Middle Aged; Multiple Sclerosis; Myelin Sheath; Saxitoxin; Sodium Channels