Nonsurgically induced disuse muscle atrophy and neuromuscular dysfunction upregulates alpha7 acetylcholine receptors

Abstract

Previous models of muscle disuse have invariably used surgical methods that require the repetitive application of plaster casts. A method of disuse atrophy that does not require such repetitive applications is described herein. Modified plastic pipette tubing was applied to a single hindlimb (mouse), from thigh to foot, resulting in immobilization of the knee in the extension position, and the ankle in the plantar flexion position. This method resulted in the loss of soleus muscle to 11%, 22%, 39%, and 45% of its original mass at 3, 7, 14, and 21 days, respectively, in association with a significant decrease of tibialis twitch (25%) and tetanic tensions (26%) at 21 days, compared with the contralateral side and (or) sham-immobilized controls. Immunohistochemical analysis of the soleus using fluorescent α-bungarotoxin revealed a significant increase in the number of synapses per unit area (818 + 31 compared with 433 + 16/mm2) and an increase in muscle fibers per unit area (117 compared with 83/mm2), most likely related to the atrophy of muscle fibers bringing synapses closer. A 3-fold increase in alpha7 acetylcholine receptor (α7AChR) protein expression, along with increased expression of α1AChR subunit in the immobilized side compared with the contralateral side was observed. The physiology and pharmacology of the novel finding of upregulation of α7AChRs with disuse requires further study.