Stretching Ameliorates Skeletal Muscle Hypoexcitability during the Early Stage of Denervation

Abstract

Denervation (DEN) results in a rapid loss of excitability in skeletal muscles. We here examined the effects of stretching (STR) on muscle hypoexcitability during the early stage of denervation. Wistar rats were divided into the DEN and DEN+STR groups. DEN was induced unilaterally by cutting the sciatic nerve and was developed for 2 days. Denervated plantar flexor (PF) muscles were maximally stretched with nonelastic tape to keep an ankle joints at 60° dorsiflexion for 0.5 or 12 hours per day. There was a remarkable increase in in situ chronaxie in PF muscles from the DEN group. This was accompanied by decreased endplate area and mRNA levels of acetylcholinesterase (AChE) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in denervated gastrocnemius muscles. Moreover, depolarization-induced force production, but not maximal Ca²⁺-activated force, was markedly reduced in mechanically skinned fibres from denervated gastrocnemius muscles. Importantly, DEN-induced prolonged chronaxie and decreased endplate area, but not depolarization-induced force depression in skinned fibres and reduced mRNA levels of AChE and PGC-1α, were alleviated by daily STR treatment. Our results suggest that mechanical load induced by STR inhibits post-synaptic dysfunction and hence an activation failure in early denervated skeletal muscle. Thus, STR can be used to preserve muscle contractile function during early stage of denervation.