Computer modelling of the properties of nerve excitability (threshold electrotonus and recovery cycle).

<p><b>A-D</b>, The results from nerve excitability test of motor and sensory axons from NC2 (the meaning of symbols are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141935#pone.0141935.g001" target="_blank">Fig 1</a>) and patients. <b>E and F</b>, The gray lines are the simulated excitability curves for NC2, and the orange lines are for patients. For motor axons, the nodal sodium permeability is reduced from 4.1 to 3.75 (cm^-3 x 10⁹) to simulate the test results shown in <b>A</b> and <b>B</b>. Based on the motor nerve NET data from patients, we identified three parameters with little discrepancy that are the leak current conductance (1.38 to 2.7 nS), hyperpolarization-activated conductance (6.05 to 7.85 nS) and decrease of nodal transient sodium current permeability (4.1 to 3.75 cm^-3 x 10⁹). Best fits with changes in these parameters can reduce the discrepancy of 21.7%, 20.9% and 19.8%, respectively. Reduction in sodium currents permeability (4.1 to 3.75 cm^-3 x 10⁹) causes highest increase of threshold (7.3%), which is the characteristic feature in motor NET findings of patients. In contrast, increase of leak current or hyperpolarization-activated conductance would cause a prominent reduction of threshold elevation after hyperpolarization in I/V curve, which is not found in our patients (Data not shown). <b>G and H</b>, For sensory axon simulation, increase of capacitance upon internodal membrane from 0.196 to 0.273 nF is used to simulate the tested results in <b>C</b> and <b>D</b>. Two parameters in computer models may be changed to fit the results from sensory NET findings from patients. They are the pumping currents and internodal capacitance. With 8.5% reduction of transient sodium channel permeability, increase of the nodal and internodal pumping currents from 11.8 to 21.7 pA and of the internodal capacitance from 0.196 to 0.273 nF could reduce the discrepancy of 68.4% and 38.7%, respectively. The increase in pumping currents, however, is physiologically difficult to envisage in our case (See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141935#sec013" target="_blank">Discussion</a>). The findings with decrease of the TE_{h(slope 101-140ms)} and protracted the time to overshoot in hyperpolarization TE as shown in patients NET findings (in part <b>C</b>) can be replicated in the model with increased internodal capacitance. Similarly, the modeling with increased internodal capacitance also well describes the increase of refractoriness and superexcitability from patients (in part <b>D)</b>. The computer simulation demonstrates the likelihood of early changes in nodal sodium conductance and internodal capacitance, but would by no means rule out concomitant minor alterations in the other axonal membrane conductances. The error bars indicate the standard error of mean (S.E.M.). The lines in part-A to -D are drawn by hand.