title: Neuromuscular adaptations to respiratory muscle inactivity.
abstract: Cervical spinal cord injury results in significant functional impairment. It is important to understand the neuroplasticity in response to inactivity of respiratory muscles in order to prevent any associated effects that limit functional recovery. Recent studies have examined the mechanisms involved in inactivity-induced neuroplasticity of diaphragm motor units. Both spinal hemisection at C2 (C2HS) and tetrodotoxin (TTX)-induced phrenic nerve blockade result in diaphragm paralysis and inactivity of axon terminals. However, phrenic motoneurons are inactive with C2HS but remain active after TTX. Diaphragm muscle fibers ipsilateral to C2HS display minimal changes post-injury. Neuromuscular transmission is enhanced following C2HS but impaired following TTX. Synaptic vesicle pool size at diaphragm neuromuscular junctions increases after C2HS, but decreases after TTX. Thus, inactivity-induced neuromuscular plasticity reflects specific adaptations that depend on inactivity at the motoneuron rather than at axon terminals or muscle fibers. These results indicate that neuromuscular transmission and functional properties of diaphragm fibers can be maintained after spinal cord injury, providing a substrate for functional recovery and/or specific therapeutic approaches such as phrenic pacing.
authors.affiliation: Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, United States. mantilla.carlos@mayo.edu
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Mantilla
authors.forename: Gary C
authors.initials: GC
authors.lastname: Sieck
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000779:Anesthetics, Local / Q000009:adverse effects; D000818:Animals; D002574:Cervical Vertebrae / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D003964:Diaphragm / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology; D012132:Respiratory Muscles / Q000187:drug effects / Q000503:physiopathology*; D012133:Respiratory Paralysis / Q000209:etiology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000009:adverse effects
chemical_list: D000779:Anesthetics, Local; D013779:Tetrodotoxin