Ouabain reverses conduction disturbances in single demyelinated nerve fibers

Abstract

Symptoms in patients with demyelinating disorders are associated with 3 important conduction abnormalities: complete conduction block, rate-dependent conduction block, and slowed impulse conduction. The recent observation that the electrogenic Na/K pump causes the nerve membrane hyperpolarization responsible for rate-dependent conduction block in demyelinated axons raises the possibility that focal inhibition of the pump may reverse the rate-dependent block. Since the pump is also responsible for maintaining part of the resting membrane potential, pump inhibition might have an additional effect of reversing the complete conduction block by reducing the threshold. We have demonstrated that inhibition of the pump by topical application of ouabain, a short-acting cardiac glycoside, reverses the conduction abnormalities in acutely demyelinated single rat ventral root axons by reducing the threshold of transmission. Ouabain or other cardiac glycosides show potential promise as agents for trial in the symptomatic treatment of patients with MS and other demyelinating disorders.