Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation

Nature Communications, 2020 · DOI: https://doi.org/10.1038/s41467-019-14063-8 · Published: February 21, 2020

Simple Explanation

This study investigates the factors that prevent muscle atrophy following denervation and promote successful reinnervation. The research demonstrates that activating nicotinic acetylcholine receptors (nAChRs) with acetylcholine (ACh) released from motoneurons is sufficient to prevent denervation-induced changes. The findings suggest that nAChRs and connexin hemichannels could be targeted for therapeutic interventions in conditions with reduced neuromuscular transmission.

Study Duration

Not specified

Participants

Mice

Evidence Level

Level: Not specified, Study type: In vitro and In vivo experiments

Key Findings

1
Acetylcholine (ACh) and its analogs repress the expression of connexin43 and connexin45 hemichannels, which are associated with muscle atrophy.
2
Knockout or knockdown of connexin43/45 hemichannels increased the innervation of muscle fibers by dorsal root ganglion neurons in co-culture studies.
3
ACh released by motoneurons has a previously unknown function, independent of myofiber contraction, in preventing muscle atrophy.

Research Summary

Denervation of skeletal muscles leads to atrophy, marked by cellular changes like increased plasma membrane permeability and accelerated protein catabolism. The study aimed to identify factors preventing these changes and promoting reinnervation. The research found that activation of nicotinic acetylcholine receptors (nAChRs) by acetylcholine (ACh) released from motoneurons prevents denervation-induced changes. ACh and its analogs repressed connexin43/45 hemichannel expression, reducing muscle atrophy. The study concludes that ACh, acting through nAChRs, prevents connexin-mediated atrophy and that Cx43/45 hemichannel activity is detrimental to reinnervation. These findings suggest potential therapeutic targets for conditions with impaired neuromuscular transmission.

Practical Implications

Therapeutic Targets

nAChRs and connexin hemichannels are potential therapeutic targets for pathological conditions with reduced neuromuscular transmission.

Reinnervation Improvement

Inhibition of sarcolemmal Cx43 and 45 HCs could improve the reinnervation of skeletal muscles.

Understanding Muscle Atrophy

ACh's role in preventing connexin-mediated atrophy provides insights into the molecular mechanisms of muscle atrophy.

Study Limitations

1
The molecular mechanisms responsible for suppression sarcolemmal Cx HCs expression remain uncertain.
2
Further studies are needed to thoroughly understand the role (s) of intracellular signaling pathways downstream of nAChR.
3
The specific myokines responsible for the deleterious effects of denervated myoﬁbers on axon growth and innervation are not identified.

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