A novel ex vivo model of nerve-induced skeletal muscle contraction

Skeletal muscle is a highly organized tissue that possesses the ability to contract and that exerts metabolic, endocrine and paracrine functions. Previous studies explored these functions through in vitro models, computational analyses, and endpoint measurements. To include the cellular complexity that modulates muscle endocrine and paracrine functions, and to allow us to study the kinetics of released and/or depleted factors, we developed a novel setup for ex vivo contraction of whole skeletal muscle. Ex vivo contraction of the Extensor Digitorum Longus (EDL) induced by nerve stimulation resulted in a reduction of relative maximal force, an increase in glucose uptake and lactate release, and a depletion of muscle glycogen content, without any overt signs of muscle damage. After cessation of contraction, relative maximal force recovered, and IL6 was secreted. Taken together, we have developed and validated a new model of ex vivo contraction that includes the full functional complexity of the muscle and mimics the in vivo physiological response to contraction. Importantly, this model supports for the first time to study the kinetics of the endocrine and paracrine response of the muscle to contraction, and to investigate its effects on various cell-types in vitro.