DISRUPTION AND REORGANIZATION OF SODIUM-CHANNELS IN EXPERIMENTAL ALLERGIC NEURITIS

The axonal distribution of voltage-dependent Na+ channels was determin ed during inflammatory demyelinating disease of the peripheral nervous system. Experimental allergic neuritis was induced in Lewis rats by a ctive immunization. In diseased spinal roots Na+ channel immunofluores cence at many nodes of Ranvier changed from a highly focal ring to a m ore diffuse pattern and, as the disease progressed, eventually became undetectable. The loss of nodal channels corresponded closely with the development of clinical signs. Electrophysiological measurements and computations showed that a lateral spread of nodal Na+ channels could contribute significantly to temperature sensitivity and conduction blo ck. During recovery new clusters of Na+ channels were seen. In fibers with large-scale demyelination, the new aggregates formed at the edges of adhering Schwann cells and appeared to fuse to form new nodes. At nodes with demyelination limited to paranodal retraction, Na+ channels were often found divided into two symmetric highly focal clusters. Th ese results suggest that reorganization of Na+ channels plays an impor tant role in the pathogenesis of demyelinating neuropathies. (C) 1998 John Wiley & Sons, Inc.