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Dynamical study of \(\mathbf{Na }_{{\varvec{v}}}\) channel excitability under mechanical stress

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Abstract

Alteration of \(\hbox {Na}_v\) channel functions (channelopathies) has been encountered in various hereditary muscle diseases. \(\hbox {Na}_v\) channel mutations lead to aberrant excitability in skeletal muscle myotonia and paralysis. In general, these mutations disable inactivation of the \(\hbox {Na}_v\) channel, producing either repetitive action potential firing (myotonia) or electrical dormancy (flaccid paralysis) in skeletal muscles. These “sick-excitable” cell conditions were shown to correlate with a mechanical stretch-driven left shift of the conductance factors of the two gating mechanisms of a fraction of \(\hbox {Na}_v\) channels, which make them firing at inappropriate hyperpolarised (left-shifted) voltages. Here we elaborate on a variant of the Hodgkin–Huxley model that includes a stretch elasticity energy component in the activation and inactivation gate kinetic rates. We show that this model reproduces fairly well sick-excitable cell behaviour and can be used to predict the parameter domains where aberrant excitability or paralysis may occur. By allowing us to separate the incidences of activation and inactivation gate impairments in \(\hbox {Na}_v\) channel excitability, this model could be a strong asset for diagnosing the origin of excitable cell disorders.

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Acknowledgements

The authors gratefully acknowledge financial support from China Scholarship Council. This project was supported by the National Science Foundation of China (81590953, 81574053, 8157150277), the National Program on Key Basic Research Project (973 Program) (2012CB518502), the Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function (14DZ2260500) and the National Science Foundation of Shanghai (15441903800). This work was also supported by the Centre National de la Recherche Scientifique, l’Ecole Normale Superieure of Lyon and the University of Bordeaux.

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Authors and Affiliations

  1. Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function, Department of Aeronautics and Astronautics, Fudan University, Shanghai, 200433, China

    Q. X. Ma & G. H. Ding

  2. LOMA, CNRS, UMR 5798, Université de Bordeaux, 51 Cours de la Libération, 33405, Talence, France

    A. Arneodo & F. Argoul

  3. Laboratoire de Physique, ENS Lyon, CNRS UMR5672, Université de Lyon, 46 Allée d’Italie, 69364, Lyon, France

    A. Arneodo & F. Argoul

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  1. Q. X. Ma
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Correspondence to F. Argoul.

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Ma, Q.X., Arneodo, A., Ding, G.H. et al. Dynamical study of \(\mathbf{Na }_{{\varvec{v}}}\) channel excitability under mechanical stress. Biol Cybern 111, 129–148 (2017). https://doi.org/10.1007/s00422-017-0712-3

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