Neuromuscular junction instability and altered intracellular calcium handling as early determinants of force loss during unloading in humans

Few days of unloading are sufficient to induce a decline of skeletal muscle mass and function; notably, contractile force is lost at a faster rate than mass. The reasons behind this disproportionate loss of muscle force are still poorly understood. We provide strong evidence of two mechanisms only hypothesized until now for the rapid muscle force loss in only 10 days of bed rest. Our results show that an initial neuromuscular junction instability, accompanied by alterations in the innervation status and impairment of single fibres sarcoplasmic reticulum function contribute to the loss of contractile force in front of a preserved  myofibrillar function and central activation capacity. Early onset of neuromuscular junction instability and impairment in calcium dynamics involved in E-C coupling are proposed as eligible determinants to the greater decline in muscle force than in muscle size during unloading.