Mechanisms defining the action potential abnormalities in simulated amyotrophic lateral sclerosis

Abstract

The present study investigates action potential abnormalities obtained in simulated cases of three progressively greater degrees of uniform axonal dysfunctions. The kinetics of the currents, defining the action potential propagation through the human motor nerve in the normal and abnormal cases, are also given and discussed. These computations use our previous multi-layered model of the myelinated motor axon, without taking into account the aqueous layers within the myelin sheath. The results show that the classical "transient" Na(+) current contributes mainly to the action potential generation in the nodal segments, as the contribution of the nodal fast and slow potassium currents to the total nodal ionic current is negligible. However, the ionic channels beneath the myelin sheath are insensitive to the short-lasting current stimuli and do not contribute to action potential generation in the internodal compartments along the fibre length. The slight changes obtained in the currents underlying the generated action potentials in the three amylotropic lateral sclerosis cases are consistent with the effect of uniform axonal dysfunction along the fibre length. Nevertheless that the uniform axonal dysfunction progressively increases in the nodal and internodal segments of each next simulated amylotropic lateral sclerosis case, the action potentials cannot be regarded as definitive indicators for the progressive degrees of this disease.