Axonal coding of action potentials in demyelinated nerve fibers.
Conduction in individual axons of Xenopus has been measured optically in response to short trains of stimuli, following demyelination of the sciatic nerve. In many cases the initial action potential in a burst is absent. Failure may also occur later in the train, resulting in a profound alteration of signal coding by the axon. Integration leading to delayed transmission occurred at the heminode forming the proximal border of the demyelinated zone, as well as at new nodes of Ranvier forming in remyelinating axons. This process appeared to involve a depolarizing afterpotential and seemed to be analogous to the threshold changes involved in superexcitability. Axonal coding was very sensitive to small changes in the stimulus pattern. Neither 1 mM tetraethylammonium ion, which blocks nodal and Ca2+ activated K+ channels, nor 1 mM 4-aminopyridine, which blocks fast internodal K+ channels, prevented loss of the initial spike in a burst. Similarly, neither block of Ca2+ channels by Cd2+ nor lowering of Cl- had a notable effect. Ouabain, on the other hand, had small but possibly significant effects on responses to repetitive stimuli. A computational model was used to test mechanisms involving passive cable properties. Lowering the myelin resistance and the nodal leakage conductance, in accord with recent evidence from intracellular recordings, reproduced many of the results and was accurate with respect to stimulus frequency, temperature and sensitivity to average potential. The coding of action potentials observed here may have clinical consequences in demyelinating diseases such as multiple sclerosis.
Department of Physiology, University of Rochester Medical Center, NY 14642.
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D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D004553:Electric Conductivity; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008959:Models, Neurological; D009412:Nerve Fibers / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D011901:Ranvier's Nodes / Q000502:physiology; D012584:Sciatic Nerve / Q000502:physiology*; D009435:Synaptic Transmission; D013696:Temperature; D014981:Xenopus