Theoretical predication of temperature effect on conducting processes in simulated amyotrophic lateral sclerosis at 20-40[Formula: see text]C.

Abstract

The present study investigates action potential abnormalities in previously simulated cases of amyotrophic lateral sclerosis, termed as ALS1, ALS2 and ALS3, respectively, when the temperature is changed from 20[Formula: see text]C to 42[Formula: see text]C.These ALS cases are modeled as three progressively severe axonal abnormalities. The effects of temperature on the kinetics of currents, defining action potentials in the normal and abnormal cases, are also given and discussed. These computations use our temperature-dependent multi-layered model of human motor nerve fibers. The results show that the classical "transient" sodium current ([Formula: see text]) contributes mainly to the nodal action potential generation in the normal and abnormal cases for the temperature range of 20-39[Formula: see text]C, as the contribution of fast and slow potassium currents ([Formula: see text] and [Formula: see text]) to the total ionic current ([Formula: see text]) is negligible. However, the contribution of [Formula: see text] and [Formula: see text] to the membrane repolarization is enhanced at temperatures higher than 39[Formula: see text]C, especially at 42[Formula: see text]C, and the after-potentials are hyperpolarized in the normal and ALS1 cases, while, they are re-depolarized in the ALS2 and ALS3 cases. The ionic channels beneath the myelin sheath are insensitive to the short-lasting current stimuli and do not contribute to the internodal action potential generation for the normal and abnormal cases in the whole investigated temperature range. Nevertheless that the uniform axonal dysfunction progressively increases in the nodal and internodal segments of each next simulated ALS case, the action potentials cannot be regarded as definitive indicators for the progressive degrees of this disease, when the temperature is changed from 20[Formula: see text]C to 42[Formula: see text]C. However, the results are essential for the interpretation of mechanisms of action potential measurements in ALS patients with symptoms of cooling, warming and fever, which can result from alteration in body temperature. Our results also suggest that the conducting processes in patients with ALS are in higher risk during hyperthermia ([Formula: see text]C) than hypothermia ([Formula: see text]C).