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bioRxiv · 10.1101/2022.06.01.494421

Motor unit dysregulation following 15 days of unilateral lower limb immobilisation

Inns, T. B.·Bass, J. J.·Hardy, E. J. O.·Stashuk, D. W.·Atherton, P. J.·Phillips, B. E.·Piasecki, M.
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Abstract

Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular EMG (iEMG) recorded from the vastus lateralis during knee extensor contractions normalised to maximal voluntary contraction (MVC) pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in MU discharge and MU potential (MUP) characteristics. Vastus lateralis (VL) CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised VL. Parameters of MUP size were largely reduced with immobilisation, while neuromuscular junction (NMJ) transmission instability increased, and MU firing rate decreased at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU discharge rate and instability of transmission at the NMJ which may underpin the disproportionate reductions of strength relative to muscle size. Key pointsO_LIMuscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation. C_LIO_LIThe reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to the muscle. C_LIO_LIWe have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size was associated with suppressed motor unit firing rate and increased markers of neuromuscular junction transmission instability. C_LIO_LIThese central and peripheral motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans. C_LI

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Inns, T. B., Bass, J. J., Hardy, E. J. O., Stashuk, D. W., Atherton, P. J., Phillips, B. E., Piasecki, M.. 2022-06-03. Motor unit dysregulation following 15 days of unilateral lower limb immobilisation. https://doi.org/10.1101/2022.06.01.494421

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