Overcoming conduction failure in demyelinated nerve fibres by prolonging action potentials

Abstract

LOSS of myelin from central or peripheral myelinated nerve fibres results in conduction delays, increased refractoriness and, above all, conduction block^1,2. Conduction failure could result either because a demyelinated axon is electrically inexcitable, or because the limited current available from a normal node is insufficient to excite it. Because continuous conduction along demyelinated internodes has been observed³, it seems likely that demyelinated axons in general are able to conduct impulses, but that the impedance mismatch at the junction of normal and demyelinated axon usually prevents the realisation of this ability. In support of this, two factors have been shown to improve transmission in experimental demyelination and also, transiently, in multiple sclerosis patients: lowered calcium ion concentration^4,5, which reduces the threshold for nerve excitation, and lowered temperature^6,7, which prolongs the action potential and thereby increases the time integral of current available to depolarise and excite the demyelinated axon. To test the suggestion that a drug that specifically prolongs the action potential might prove useful in the therapy of demyelinating diseases⁸, we have compared the effects of temperature and a scorpion venom on transmission in single fibres through a demyelinating lesion in rat spinal roots.