Denervation versus pre- and postsynaptic muscle immobilization: Effects On acetylcholine- and muscle-specific tyrosine kinase receptors.
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.
Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675, München, Germany.
Christopher
C
Kramer
Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Klinikum rechts der Isar, München, Germany.
Saida
S
Zoubaa
Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675, München, Germany.
Alexander
A
Kretschmer
Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675, München, Germany.
Denis
D
Jordan
Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675, München, Germany.
Manfred
M
Blobner
Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675, München, Germany.
Heidrun
H
Fink
D000818:Animals; D001835:Body Weight; D003714:Denervation; D003964:Diaphragm / Q000502:physiology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000196:embryology / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D011950:Receptors, Cholinergic; D013779:Tetrodotoxin; D020794:Receptor Protein-Tyrosine Kinases
MuSK; motor endplate; neuromuscular transmission; nicotinic acetylcholine receptors; respiratory muscles