NODAL NA-CHANNEL DISPLACEMENT IS ASSOCIATED WITH NERVE-CONDUCTION SLOWING IN THE CHRONICALLY DIABETIC BB()W RAT - PREVENTION BY ALDOSE REDUCTASE INHIBITION/

Chronic nerve conduction slowing in experimental diabetic neuropathy h as been associated with decreased nodal Na+ permeability and an ultras tructurally identifiable loss of axo-glial junctions, which comprise t he paranodal voltage channel barrier separating nodal Na- channels fro m paranodal K- channels, In human and experimental diabetic neuropathy these structural changes of the paranodal apparatus correlate closely with the nerve conduction defect. The present immunocytochemical stud y of the alpha-subunit of the Na- channel examined whether the breach of the voltage channel barrier may account for a shift in the distribu tion of Na- channels explaining decreased nodal Na+ permeability. Biob reeding Wister (BB/W) rats diabetic for 4-8 months showed a progressiv e redistribution of nodal Na+ channels across the paranodal barrier in to the paranodal and internodal domains which was associated with chro nic nerve conduction slowing. The present data suggest that structural damage to the paranodal barrier system in diabetic nerve facilitates the lateral displacement of Na+ channels from the nodal axolemma there by diminishing their nodal density and the nodal Na- permeability asso ciated with the chronic nerve conduction defect in experimental diabet es. These abnormalities were prevented by the treatment with an aldose reductase inhibitor, belonging to a class of drugs that, in neuropath ic patients, improves nerve-conduction velocity and repairs axo-glial dysjunction of the paranodal apparatus.