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To expand our studies on accommodation in human motor nerve axons, the effects of temperature on polarizing nodal and internodal electrotonic potentials and their current kinetics are investigated. The computations use our temperature dependent multi-layered model of the myelinated human motor nerve fiber and the temperature is increased from 20°C to 42°C. The results show that for temperatures from 28°C to 37°C, the polarizing electrotonic potentials almost coincide, as the kinetics of their ionic currents is changed a little. The normal (at 37°C) resting membrane potential is further depolarized or hyperpolarized during hypothermia (≤ 25°C) or hyperthermia (≥ 40°C), respectively and its change is determined by the flow of ionic currents through the internodal axolemma during the polarizing current stimuli. The polarizing electrotonic potentials are more altered during hypothermia and are most altered during hyperthermia. During hyperthermia, the depolarizing nodal and internodal electrotonic potentials are determined by the nodal slow (I_Ks) and internodal fast (I_Kf) and slow (I_Ks) potassium currents. The hyperpolarizing internodal electrotonic potentials are determined by the activation of internodal channels, which are different during hyperthermia at 40°C and 42°C. These potentials are determined by the internodal I_Ks current at 40°C and by the internodal inward rectifier (I_IR) and leakage (I_Lk) currents at 42°C. The difference in accommodation to hyperpolarizing currents during focal and uniform hyperthermia at 42°C is discussed. The present results are essential for the interpretation of mechanisms of threshold electrotonus measurements in subjects with symptoms of cooling, warming and fever, which can result from alterations in body temperature.

The effects of temperature on conducting and accommodative processes in the myelinated human motor nerve fiber were previously studied by us in the range of 20°C–42°C. To complete the cycle of our studies on adaptive processes in the fiber, the temperature effects on strength-duration time constant, rheobasic current and recovery cycle are investigated. The computations use our temperature dependent multi-layered model of the fiber and the temperature is increased from 20°C to 42°C. The results show that these excitability parameters are more sensitive to the hypothermia (≤ 25°C) and are most sensitive to the hyperthermia (≥ 40°C), especially at 42°C, than at temperatures in the range of 28°C–37°C. With the increase of temperature from 20°C to 42°C, the strength-duration time constant decreases ~ 8.8 times, while it decreases ~ 2.7% per °C in the range of 28°C–37°C. Conversely, the rheobasic current increases ~ 4.4 times from 20°C to 42°C, while it increases ~ 2.3% per °C in the range of 28°C–37°C. The behavior of relative refractory period and axonal superexcitability in a 100 ms recovery cycle is complex with the increase of temperature. The axonal superexcitability decreases with the increase of temperature during hypothermia. However, it increases rapidly with the increase of temperature during hyperthermia, especially at 42°C and a block of each applied third testing stimulus is obtained. The superexcitability period is followed by a late subexcitability period when the temperatures are in the physiological range of 32°C–37°C. The present results are essential for the interpretation of mechanisms of excitability parameter changes obtained here and measured in healthy subjects with symptoms of cooling, warming and fever, which can result from alterations in body temperature. Our present and previous results confirm that 42°C is the highest critical temperature for healthy subjects.

Decreased conducting processes leading usually to conduction block and increased weakness of limbs during cold (cold paresis) or warmth (heat paresis) have been reported in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To explore the mechanisms of these symptoms, the effects of temperature (from 20°C to 42°C) on nodal action potentials and their current kinetics in previously simulated case of 70% CIDP are investigated, using our temperature dependent multi-layered model of the myelinated human motor nerve fiber. The results show that potential amplitudes have a bifid form at 20°C. As in the normal case, for the CIDP case, the nodal action potentials are determined mainly by the nodal sodium currents (I_Na) for the temperature range of 20–39°C, as the contribution of nodal fast and slow potassium currents (I_Kf and I_Ks) to the total ionic current (Ii) is negligible. Also, the contribution of I_Kf and I_Ks to the membrane repolarization is enhanced at temperatures higher than 39°C. However, in the temperature range of 20–42°C, all potential parameters in the CIDP case, except for the conduction block during hyperthermia (≥ 40°C) which is again at 45°C, worsen: (i) conduction velocities and potential amplitudes are decreased; (ii) afterpotentials and threshold stimulus currents for the potential generation are increased; (iii) the current kinetics of action potentials is slowed and (iv) the conduction block during hypothermia (≤ 25°C) is at temperatures lower than 20°C. These potential parameters are more altered during hyperthermia and are most altered during hypothermia. The present results suggest that the conducting processes in patients with CIDP are in higher risk during hypothermia than hyperthermia.

Threshold electrotonus changes have been studied following warming to 37°C and cooling to 25°C in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To extend the tracking of these changes also during hypothermia (≤ 25°C) and hyperthermia (≥ 40°C), and to explain their mechanisms, we investigate the effects of temperature (from 20°C to 42°C) on polarizing nodal and internodal electrotonic potentials and their current kinetics in previously simulated case of 70% CIDP. The computations use our temperature-dependent multi-layered model of the myelinated human motor nerve fiber. While the changes of electrotonic potentials and their current kinetics are largely similar for the physiological range of 28–37°C, they are altered during hypothermia and hyperthermia in the normal and CIDP cases. The normal (at 37°C) resting membrane potential is further depolarized or hyperpolarized during hypothermia or hyperthermia, respectively, and the internodal current types defining these changes are the same for both cases. Unexpectedly, our results show that in the CIDP case, the lowest and highest critical temperatures for blocking of electrotonic potentials are 20°C and 39°C, while in the normal case the highest critical temperature for blocking of these potentials is 42°C. In the temperature range of 20–39°C, the relevant potentials in the CIDP case, except for the lesser value (at 39°C) in hyperpolarized resting membrane potential, are modified: (i) polarizing nodal and depolarizing internodal electrotonic potentials and their defining currents are increased in magnitude; (ii) inward rectifier (I_IR) and leakage (I_Lk) currents, defining the hyperpolarizing internodal electrotonic potential, are gradually increased with the rise of temperature from 20°C to 39°C, and (iii) the accommodation to long-lasting hyperpolarization is greater than to depolarization. The present results suggest that the electrotonic potentials in patients with CIDP are in high risk for blocking not only during hypothermia and hyperthermia, but they are also in risk for worsening at the temperature range of 37–39°C.

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${}^{\circ }$C to 42${}^{\circ }$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 ($I_{\mathrm{\text{Na}}}$) contributes mainly to the nodal action potential generation in the normal and abnormal cases for the temperature range of 20–39${}^{\circ }$C, as the contribution of fast and slow potassium currents ($I_{\mathrm{\text{Kf}}}$ and $I_{\mathrm{\text{Ks}}}$) to the total ionic current ($I_i$) is negligible. However, the contribution of $I_{\mathrm{\text{Ks}}}$ and $I_{\mathrm{\text{Kf}}}$ to the membrane repolarization is enhanced at temperatures higher than 39${}^{\circ }$C, especially at 42${}^{\circ }$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${}^{\circ }$C to 42${}^{\circ }$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 ($\ge 40^{\circ }$C) than hypothermia ($\le 25^{\circ }$C).