Computer simulation of action potentials and afterpotentials in mammalian myelinated axons: the case for a lower resistance myelin sheath

Depolarizing afterpotentials, recorded in peripheral nerves [Barrett and Barrett (1982) J. Physiol., Lond. 323, 117-144] and spinal axons [Blight and Someya (1985) Neuroscience 15, 1-12], have been interpreted as representing passive discharge of axolemmal capacitance. This interpretation requires a lower resistance pathway through the myelin sheath than previous measurements have suggested. A computer model was used to examine the contribution of the electrical characteristics of nerve fibers to action potential conduction and afterpotential generation. The model consisted of a resistance-capacitance network representing a chain of 20 internodes. The resistances of node, internode and myelin sheath, deduced from observations in the accompanying paper, [Blight and Someya (1985) Neuroscience, 15] were found to produce suitable length and time constants, and prolonged afterpotentials, when inserted into the model. Similar length and time constants were found using a conventional model of the axon, based on measurements from isolated peripheral fibers, but this did not reproduce the afterpotentials. Action-potential conduction velocity is enhanced by reducing the time constant and increasing the length constant. The problem of minimizing the internodal time constant was met in the conventional model through the low parallel resistance of the node, while in the new model it was met by reducing the resistance of the myelin sheath. The latter strategy required the nodal leakage resistance to be higher than values from single fiber measurements (ca 250 M omega rather than ca 50 M omega) in order to maintain the length constant similar to the conventional model. Simulation of the recorded potentials required the resistance of the myelin lamellae to be approx. 100 omega cm2. The model quantitatively reproduced the voltage response of the axon to injected current pulses and to propagated action potentials, using Frankenhaeuser-Huxley kinetics. [Frankenhaeuser and Huxley (1964) J. Physiol., Lond. 171, 302-315; Frankenhaeuser and Moore (1963) J. Physiol., Lond. 169, 431-437]. The short duration components of the afterpotential, observed in mammalian recordings were reproduced by assuming a leakage pathway in the myelin sheath, at the impalement site. The calculated lower resistance of the myelin sheath was such that it minimized the effective internodal time constant for a given nodal resistance. This appears to free the myelinated fiber from the alternative requirement for a high nodal leakage conductance.(ABSTRACT TRUNCATED AT 400 WORDS)