Adaptations de la commande nerveuse du muscle en fonction des conditions dynamiques de sa contraction

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Propriétés électrophysiologiques des canaux sodiques du muscle strié squelettique et contrainte mécanique

Les canaux sodiques dépendants du potentiel (Na) sont responsables du déclenchement et de la propagation du potentiel d action musculaire. Ils participent ainsi à l excitabilité de la fibre musculaire et à ses propriétés contractiles. L immobilisation musculaire induit des changements du phénotype contractile. Nous avons étudié l effet de 4 et 8 semaines d immobilisation du muscle Peroneus Longus (PL) à sa longueur optimale, sur ses propriétés contractiles et les propriétés électrophysiologiques de ses canaux sodiques. Après 4 semaines d immobilisation, les propriétés contractiles du muscle présentent une conversion vers un phénotype plus rapide avec un retour partiel vers les propriétés du muscle contrôle après 8 semaines d immobilisation. Les courants provenant du canal sodique de type 1.4 (Nav 1.4) augmentent puis diminuent, alors que les courants et l expression du Nav 1.5 diminuent continuellement au cours de l immobilisation. Ces résultats indiquent que la possibilité pour un muscle de se raccourcir ou de s allonger est indispensable pour conserver son phénotype contractile et maintenir le ratio Nav 1.4/ Nav 1.5. L expression du Na 1.4 est corrélée avec le phénotype rapide du muscle. Pour étudier l hypothèse d une participation des Na au phénotype contractile de la fibre musculaire, des fibres dissociées de muscles de la patte de rats Wistar ont été étudiées par la technique du macropatch-clamp, puis l isoforme de chaîne lourde de myosine (CLM) qu elles exprimaient a été déterminé par électrophorèse SDS-PAGE. Dans les fibres de PL, le courant sodique maximal (Imax) et la conductance sodique maximale (gNa max) augmentent selon le schéma suivant: type I->IIa->IIx->IIb de CLM. Ce résultat est cohérent avec une activation progressive des différents types de fibres (du type lent vers le type rapide) dans un muscle mixte comme le PL. En se contractant, le muscle soumet sa membrane à des variations de longueur donc de tension. Il est licite de s intéresser à l effet de ces variations de tension sur le fonctionnement des protéines membranaires comme les Nav. En configuration patch-clamp, nous avons appliqué, dans un ordre aléatoire, différents niveaux de dépression (0, -10, -20, -30 mmHg) sur la membrane. Le courant sodique maximal (Imax) et la conductance sodique maximale augmentent avec le niveau de dépression. Les courbes d activation sont décalées vers les potentiels négatifs avec la dépression. Le processus d inactivation lente des Nav est augmenté par la dépression. Sur le plan fonctionnel, ces résultats sont en faveur d une participation des Nav au phénomène de stretch-activation (augmentation de la force produite d un muscle par son étirement préalable). Toutefois la diminution du nombre de canaux activables (inactivation lente) par l étirement membranaire permet, à moyen terme, de moduler l excitabilité et donc la fatigabilité du muscle.Voltage-gated sodium channels (Nav) are involved in the triggering and the propagation of muscle action potential. The electrophysiological properties of Nav determine muscle excitability and influence the contractile properties of muscle. Muscle immobilization leads to modification in its fast/slow contractile phenotype. Therefore, we studied the effects of single immobilization on the contractile and the electrophysiological properties of Na, in rat muscle Peroneus Longus (PL). After 4 weeks of immobilization, PL shows a faster phenotype with partial recovery to control phenotype between 4 and 8 weeks of immobilization. Using the patch-clamp technique, sodium currents from Nav 1.4 displays a transitory increase alter 4 weeks of immobilization, whereas Nav 1.5 currents decrease continuously throughout immobilization. Our results indicate that a muscle immobilized at optimal functional length with the preservation of neural inputs, exhibits a transient fast phenotype conversion. Nav 1.4 expression and current are related to the contractile phenotype variation through muscle excitability. The myosin heavy chain (MHC) isoform determines the shortening velocity of muscle fibre. Whole muscle, even if selected according to its predominant mechanical properties ( slow or fast ), exhibits heterogeneous MHC composition. Since the properties of Na, are different between fast and slow muscles, we hypothesised that the electrophysiological properties of Na, could be related to MEC isoform expression in single muscle fibre. Alter patch-clamp recordings, single fibres were identified by SDS-PAGE electrophoresis according to their myosin heavy chain isoform (slow type I and the three fast types IIa, IIx, IIb). The maximal sodium current and conductance increase according to the scheme I->IIa->IIx->IIb. These data are consistent with the earlier recruitment of slow fibres in a fast-mixed muscle like PL. Slow fibres have to be activated early in order to optimize the mechanical performance of the predominant fast fibres. The contraction of skeletal muscle to produce force implies length and tension variation for its membrane. The consequences of tension variation on the properties of membrane proteins such as sodium channels remain questioning. In patch-clamp configuration, different levels of depression were applied with the pipette to stretch muscle membrane and Nav. Membrane stretch increases maximal sodium current and induces a leftward shift in activation and slow inactivation curves in a dose-dependent manner. Nav are involved in the stretch-activation process through the enhancement of its activation threshold with membrane stretch.BREST-BU Médecine-Odontologie (290192102) / SudocSudocFranceF

Early Mobilization in ICU: About New Strategies in Physiotherapy’s Care

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Tumor Necrosis Factor alpha induced hypoexcitability in rat muscle evidenced in a model of ion currents and action potential.

International audienceSepsis and Tumor Necrosis Factor alpha (TNFα), a major pro-inflammatory mediator, have previously been shown to induce a decrease in the conductance of voltage-dependent sodium channels (NaV). Moreover, TNFα increased resting membrane potential, leading to hyperpolarization. NaV and resting potential are the two major factors of membrane excitability. Then we hypothesis that TNFα can decrease muscle membrane excitability. To evidence that role of TNFα, we carried out a simulation of the sodium and potassium currents and action potential (AP) of isolated muscle fibre. We used a computer model based on Hodgkin and Huxley equations, but also taking into account the sodium-potassium pump current. Our first aim was to optimise this model in control conditions according to our measurements of currents. Then the model was modified to fit the values measured experimentally in TNFα-containing medium in order to determine the modifications induced in the currents and hence in AP triggering. Our model provides a very good fit with experimental data on the ion currents. Moreover, it clearly shows that the triggering level of AP is increased in TNFα-containing medium, thus corresponding to a decreased excitability

Annexin A5 increases the cell surface expression and the chloride channel function of the ΔF508-cystic fibrosis transmembrane regulator

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Cytoprotective and antioxidant effects of the edible halophyte Sarcocornia perennis L. (swampfire) against lead-induced toxicity in renal cells.

International audienceLead (Pb) exposure is considered as a risk factor responsible for renal impairment in humans. On the other hand, the halophyte Sarcocornia perennis is a fresh vegetable crop suitable for leafy vegetable production. This study was designed to evaluate the in vitro protective activity of S. perennis against lead-induced damages in HEK293 kidney cells. Morphological and biochemical indicators were used to assess cytotoxicity and oxidative damages caused by Pb treatment on the cells. Our results showed that lead induced (1) a decrease in cell viability (MTT), (2) cell distortion and cohesion loss, (3) superoxide anion production and lipid peroxidation. Conversely, addition of S. perennis extract to the lead-containing medium alleviated every above syndrome. Thus, cell survival was increased and the production of reactive oxygen species caused by Pb treatment was inhibited. Taken together, our study revealed that S. perennis has potent cytoprotective effect against Pb-induced toxicity in HEK 293 cell. Such action would proceed through the decrease in ROS levels and resulting oxidative stress, which suggests a potential interest of this halophyte in the treatment of oxidative-stress related diseases

The hamstrings are more impacted than the quadriceps after severe ankle sprain

International audienceAnkle sprains (AS) are common in the military population, with a prevalence 5 to 8 times higher than that for civilians. The aim of this study was to evaluate in patients with severe AS the impact of disuse on thigh muscle induced by unloading and immobilization due to care. This study focused on muscle trophicity and dynamometric strength. In this observational prospective study, assessments were repeated at 3 visits: close to injury, 15 and 30 days following the sprain. The injured limb was compared to the contralateral limb. A dynamometer assessment was used to monitor changes in strength and fatigue of the thigh muscles of both limbs. Isometric and isokinetic concentric evaluation of peak torque (PTiso and PTdyn), total work (Wt), and peak torque time integral (IPT) of thigh muscles. Full follow-up was obtained in 30 subjects. The injured limbs showed significant deficits in the mean (SD). The quadriceps PTiso and IPT deficits were −12.6% ± 1.9% ( P < .0001) and −13.27% ± 1.8% ( P < .0001), respectively. The quadriceps PTdyn showed a significant deficit since V2 (−12.2.5% ± 2.0). The quadriceps Wt presented a significant deficit of −4.2% ± 2.4 ( P < .0007) at 1 month. The hamstring PTdyn deficit presented a mean loss of −16.5% ± 2.4% ( P < .0001). The hamstring Wt deficit was −13.7% ± 2.3% ( P < .001). The analysis of variance showed that the grade of the sprain had a significant effect on the quadriceps PTq deficit ( P < .016) but not the type of discharge. Our study showed that disuse leads to a significant deficit in the strength of knee muscles within 1 month. It is noteworthy that the hamstrings are more affected than the quadriceps. The rehabilitation protocol to prevent the risk of iterative ankle injuries and secondary knee injuries should incorporate early training of both quadriceps and hamstrings