Denervation versus pre‐ and postsynaptic muscle immobilization: Effects On acetylcholine‐ and muscle‐specific tyrosine kinase receptors

Abstract

Functional immobility of the diaphragm by mechanical ventilation impairs neuromuscular transmission and may result in ventilator-induced diaphragmatic dysfunction. We compared 3 diaphragmatic immobilization models with respect to their effects on expression of adult and fetal acetylcholine receptors (AChRs), muscle-specific receptor tyrosine kinase (MuSK), and muscle fiber morphology. Diaphragms of rats were immobilized by either: (1) phrenicotomy; (2) presynaptic tetrodotoxin nerve blockade; or (3) postsynaptic polyethylene orthosis. AChR subtypes and MuSK were quantified by Western blot and immunohistochemistry. Muscle fiber morphology was evaluated by hematoxylin-eosin staining. Adult AChRs remained unchanged, whereas fetal AChRs and MuSK were upregulated in all models. Denervation induced the strongest changes in muscle morphology. Each diaphragm immobilization model led to severe morphologic and postsynaptic receptor changes. Postsynaptic polyethylene orthosis, a new model with an intact and functioning motor unit, best reflects the clinical picture of a functionally immobilized diaphragm. Muscle Nerve 55: 101-108, 2017.