Disruption and reorganization of sodium channels in experimental allergic neuritis.
The axonal distribution of voltage-dependent Na+ channels was determined during inflammatory demyelinating disease of the peripheral nervous system. Experimental allergic neuritis was induced in Lewis rats by active immunization. In diseased spinal roots Na+ channel immunofluorescence at many nodes of Ranvier changed from a highly focal ring to a more 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 block. 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. These results suggest that reorganization of Na+ channels plays an important role in the pathogenesis of demyelinating neuropathies.
Novakovic
S D
SD
Department of Neurobiology and Anatomy, University of Rochester Medical Center, New York 14642, USA.
Levinson
S R
SR
Schachner
M
M
Shrager
P
P
D000818:Animals; D001369:Axons / Q000737:chemistry* / Q000502:physiology; D003711:Demyelinating Diseases / Q000503:physiopathology*; D004594:Electrophysiology; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D009444:Neuritis, Autoimmune, Experimental / Q000503:physiopathology*; D011901:Ranvier's Nodes / Q000737:chemistry / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology
D015222:Sodium Channels