Neuromuscular adaptations to respiratory muscle inactivity

Respir Physiol Neurobiol. 2009 Nov 30;169(2):133-40. doi: 10.1016/j.resp.2009.09.002. Epub 2009 Sep 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / physiology*
  • Anesthetics, Local / adverse effects
  • Animals
  • Cervical Vertebrae / injuries
  • Cervical Vertebrae / pathology
  • Cervical Vertebrae / physiopathology
  • Diaphragm / drug effects
  • Diaphragm / physiopathology
  • Disease Models, Animal
  • Humans
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Phrenic Nerve / drug effects
  • Phrenic Nerve / physiopathology
  • Respiratory Muscles / drug effects
  • Respiratory Muscles / physiopathology*
  • Respiratory Paralysis / etiology
  • Respiratory Paralysis / physiopathology
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology
  • Synaptic Transmission / drug effects
  • Tetrodotoxin / adverse effects


  • Anesthetics, Local
  • Tetrodotoxin