Plasticity of Conduction Processes in Demyelinated Nerve Fibers: Implications for Therapy in Multiple Sclerosis

Abstract

Until fairly recently it had always been assumed that the complete loss of myelin over one or more internodes must necessarily produce an irreversible block of impulse conduction in myelinated nerve fibers. This view is a consequence of experimental observations showing that the essential ingredients for generation of nervous activity — voltage dependent channels selective for Na ions — are normally only present at the nodes of Ranvier in mammalian and non-mammalian myelinated nerve fibers. Thus, the exposure of the internodal axon membrane which follows demyelination reveals a structure incapable of producing action potentials. A second obstacle to conduction following demyelination arises from the fact that, even if the internode were in principle excitable, the physiological function of the myelin sheath is to reduce the capacitance, and thus the amount of current necessary to charge the internodal membrane. Removal of this material, in the absence of any other changes, simply represents too great an electrical “load” on the excitation process to allow the continuation of conduction from the last normal node to the distal demyelinated segment(s).