title: Dynamical study of Νaν channel excitability under mechanical stress.
abstract: Alteration of [Formula: see text] channel functions (channelopathies) has been encountered in various hereditary muscle diseases. [Formula: see text] channel mutations lead to aberrant excitability in skeletal muscle myotonia and paralysis. In general, these mutations disable inactivation of the [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] channel excitability, this model could be a strong asset for diagnosing the origin of excitable cell disorders.
authors.affiliation: Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function, Department of Aeronautics and Astronautics, Fudan University, Shanghai, 200433, China.
authors.forename: Q X
authors.initials: QX
authors.lastname: Ma
authors.affiliation: LOMA, CNRS, UMR 5798, Université de Bordeaux, 51 Cours de la Libération, 33405, Talence, France.|Laboratoire de Physique, ENS Lyon, CNRS UMR5672, Université de Lyon, 46 Allée d'Italie, 69364, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Arneodo
authors.affiliation: Shanghai Key Laboratory for Acupuncture Mechanism and Acupoint Function, Department of Aeronautics and Astronautics, Fudan University, Shanghai, 200433, China.
authors.forename: G H
authors.initials: GH
authors.lastname: Ding
authors.affiliation: LOMA, CNRS, UMR 5798, Université de Bordeaux, 51 Cours de la Libération, 33405, Talence, France. francoise.argoul@u-bordeaux.fr.|Laboratoire de Physique, ENS Lyon, CNRS UMR5672, Université de Lyon, 46 Allée d'Italie, 69364, Lyon, France. francoise.argoul@u-bordeaux.fr.
authors.forename: F
authors.identifier: 0000-0001-9157-3565
authors.initials: F
authors.lastname: Argoul
mesh_terms: D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D015222:Sodium Channels
keywords: Bifurcations; Dynamical systems; Excitable cell disorders; Mechanical stress; Periodic firing and myotonia; Sick-excitable cell; voltage-gated channels