The loss of muscle mass and strength caused by unloading or immobilisation is common in various clinical settings, including nerve injury, joint trauma, and intensive care. Loss of strength cannot be wholly attributed to loss of mass, with, for example, power reduction being strongly associated with bed rest duration while muscle size was not (1). Mechanistic insight into muscle mass loss is well supported by data on muscle protein turnover, mitochondrial dysfunction and insulin resistance (2), yet the mechanistic underpinning of divergent losses of muscle function is less well studied. Furthermore, it is unclear if findings based on normalised strength are influenced by the consistently reported large reductions in total strength occurring alongside disuse atrophy. This research aimed to investigate functional adaptations of vastus lateralis (VL) motor units (MU) following unilateral immobilisation, sampled at forces normalised to both baseline and post-disuse maximum force.
10 young, healthy males underwent 15-days unilateral leg immobilisation. VL cross-sectional area (CSA) and knee extensor maximal voluntary contraction (MVC) were assessed pre- and post-intervention. Individual MU of the VL were sampled with intramuscular electromyography (iEMG) during isometric contractions at 25% MVC. This was performed relative to baseline MVC and the markedly lower post-immobilisation MVC. MU potential (MUP) characteristics were derived from decomposed iEMG signals using decomposition-based quantitative electromyography software. Neuromuscular junction (NMJ) transmission instability was quantified using near-fibre jiggle (3) and MU FR was measured as the frequency of observations. CSA and MVC were analysed using repeated-measures 2-way ANOVA. MUP characteristics were analysed using multi-level mixed-effects linear regression. Significance was accepted at p<0.05.
VL CSA and MVC reduced by 4.3±0.6 cm2 and 158±25.03 N respectively in the immobilised leg (both p<0.001), remaining unchanged in the control limb (p=0.99 and p=0.50). NMJ transmission instability increased in the immobilised leg using baseline MVC (β = 1.923, 95% CI: 0.508–3.337, p<0.01) and using post-disuse MVC (β = 2.04, 95% CI: 0.27–3.80, p<0.05), remaining unchanged in the control limb (p=0.67). Firing rate was reduced in the immobilised leg using baseline MVC (β = -0.925, 95% CI: -1.199 to -0.651, p<0.001) and using post-disuse MVC (β = -0.95, 95% CI: -1.34 to -0.56, p<0.001), remaining unchanged in the control limb (p=0.56).
Following immobilisation, VL size and strength were reduced as expected, with a disparity in degree of change. The greater reduction in muscle strength is partly explained by an increase in NMJ transmission instability and suppression of MU FR. Dysfunction at the NMJ may be attributable to a partial denervation and selective reinnervation process also observed in healthy ageing (4). Notably, both NMJ transmission instability and MU FR were similarly changed after immobilisation at contraction levels normalised to both baseline and post-disuse maximum force. As such, any observed reductions in individual MU function cannot be explained by the sampling of MUs recruited during lower absolute contraction levels. Rather, the current findings highlight the importance of impaired neural input to muscle in actively inhibiting force-generating capacity. Future interventions aiming to mitigate neuromuscular decline should specifically target neural input to muscle.