Citation

Barlow BM, Joos B, Trinh AK, Longtin A. Chaos Solitons Fractals 2018; 28(10): e106328.

Affiliation

Department of Physics, Centre for Neural Dynamics, University of Ottawa, 150 Louis Pasteur Priv., Ottawa, Ontario K1N6N5, Canada.

Copyright

(Copyright © 2018, Elsevier Publishing)

DOI

10.1063/1.5040288

PMID

30384659

Abstract

Mild traumatic injury can modify the key sodium (Na⁺) current underlying the excitability of neurons. It causes the activation and inactivation properties of this current to become shifted to more negative trans-membrane voltages. This so-called coupled left shift (CLS) leads to a chronic influx of Na⁺ into the cell that eventually causes spontaneous or "ectopic" firing along the axon, even in the absence of stimuli. The bifurcations underlying this enhanced excitability have been worked out in full ionic models of this effect. Here, we present computational evidence that increased temperature T can exacerbate this pathological state. Conversely, and perhaps of clinical relevance, mild cooling is shown to move the naturally quiescent cell further away from the threshold of ectopic behavior. The origin of this stabilization-by-cooling effect is analyzed by knocking in and knocking out, one at a time, various processes thought to be T-dependent. The T-dependence of the Na⁺ current, quantified by its Q _10-Na factor, has the biggest impact on the threshold, followed by Q _10-pump of the sodium-potassium exchanger. Below the ectopic boundary, the steady state for the gating variables and the resting potential are not modified by temperature, since our model separately tallies the Na⁺ and K⁺ ions including their separate leaks through the pump. When only the gating kinetics are considered, cooling is detrimental, but in the full T-dependent model, it is beneficial because the other processes dominate. Cooling decreases the pump's activity, and since the pump hyperpolarizes, less hyperpolarization should lead to more excitability and ectopic behavior. But actually the opposite happens in the full model because decreased pump activity leads to smaller gradients of Na⁺ and K⁺, which in turn decreases the driving force of the Na⁺ current.

Language: en