Changes in motor unit conduction velocity after unilateral lower‐limb suspension and active recovery are correlated with muscle ion channel gene expression

The effects of muscle disuse on the propagation of action potentials along motor unit (MU) muscle fibres, a key process for effective muscle activation and force generation, remain poorly understood. The aim of this study was to investigate changes in action potential propagation and to identify biological factors influencing these changes following unilateral lower-limb suspension (ULLS) and active recovery (AR). Eleven young males underwent 10 days of ULLS followed by 21 days of AR involving resistance exercise. Maximal force of the knee extensors (MVC), high-density surface EMG recordings and muscle biopsies of the vastus lateralis muscle were collected before ULLS, after ULLS and after AR. EMG recordings collected during submaximal isometric contractions were decomposed to estimate single-MU conduction velocity (CV). Biopsies were used to measure muscle fibre diameters via histochemical analysis and ion channel transcriptomic profiles via mRNA sequencing. The MVC declined by 29% after ULLS and returned to baseline after AR. MU CV decreased after ULLS and recovered fully, even exceeding baseline values after AR. Muscle fibre diameters did not change across the interventions and showed no correlation with MU CV. Conversely, a feature importance analysis revealed that mRNA expression levels of specific ion channel genes, particularly those involved in K⁺ transport, were correlated with MU CV at baseline and across the interventions. This study highlights the crucial role of K⁺ ion channels in influencing MU CV in humans, offering new insights into MU CV modulation and the mechanisms of changes in muscle force after disuse and active recovery.