Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle - Cellules Souches et Biothérapies Accéder directement au contenu
Article Dans Une Revue Skeletal Muscle Année : 2016

Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle

Résumé

Background The greater susceptibility to contraction-induced skeletal muscle injury (fragility) is an important dystrophic feature and tool for testing preclinic dystrophin-based therapies for Duchenne muscular dystrophy. However, how these therapies reduce the muscle fragility is not clear. Methods To address this question, we first determined the event(s) of the excitation-contraction cycle which is/are altered following lengthening (eccentric) contractions in the mdx muscle. Results We found that the immediate force drop following lengthening contractions, a widely used measure of muscle fragility, was associated with reduced muscle excitability. Moreover, the force drop can be mimicked by an experimental reduction in muscle excitation of uninjured muscle. Furthermore, the force drop was not related to major neuromuscular transmission failure, excitation-contraction uncoupling, and myofibrillar impairment. Secondly, and importantly, the re-expression of functional truncated dystrophin in the muscle of mdx mice using an exon skipping strategy partially prevented the reductions in both force drop and muscle excitability following lengthening contractions. Conclusion We demonstrated for the first time that (i) the increased susceptibility to contraction-induced muscle injury in mdx mice is mainly attributable to reduced muscle excitability; (ii) dystrophin-based therapy improves fragility of the dystrophic skeletal muscle by preventing reduction in muscle excitability.
Fichier principal
Vignette du fichier
art_10.1186_s13395-016-0096-4.pdf (2.5 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-01357455 , version 1 (30-08-2016)

Licence

Paternité

Identifiants

Citer

Pauline Roy, Fredérique Rau, Julien Ochala, Julien Messéant, Bodvael Fraysse, et al.. Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle. Skeletal Muscle, 2016, 6 (1), pp.23. ⟨10.1186/s13395-016-0096-4⟩. ⟨hal-01357455⟩
332 Consultations
160 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More