Connexin hemichannels explain the ionic imbalance and lead to atrophy in denervated skeletal muscles

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

dc.creatorCisterna-Irrazabal, Bruno Alejandro
dc.creatorVargas-Ríos, Aníbal Antonio
dc.creatorPuebla, Carlos
dc.creatorSáez-Carreño, Juan Carlos
dc.date2021-08-23T22:59:16Z
dc.date2022-07-07T14:56:16Z
dc.date2021-08-23T22:59:16Z
dc.date2022-07-07T14:56:16Z
dc.date2016
dc.date.accessioned2023-08-21T21:53:39Z
dc.date.available2023-08-21T21:53:39Z
dc.identifier1150291
dc.identifier1150291
dc.identifierhttps://hdl.handle.net/10533/252555
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8287090
dc.descriptionDenervated fast skeletal muscles undergo atrophy, which is associated with an increase in sarcolemma permeability and protein imbalance. However, the mechanisms responsible for these alterations remain largely unknown. Recently, a close association between de novo expression of hemichannels formed by connexins 43 and 45 and increase in sarcolemma permeability of denervated fast skeletal myofibers was demonstrated. However, it remains unknown whether these connexins cause the ionic imbalance of denervates fast myofibers. To elucidate the latter and the role of hemichannels formed by connexins (Cx HCs) in denervation-induced atrophy, skeletal myofibers deficient in Cx43 and Cx45 expression (Cx43(fl/fl) Cx45(fl/fl):Myo-Cre mice) and control (Cx43(f1/fl)Cx45(fl/fl) mice) were denervated and several muscle features were systematically analyzed at different postdenervation (PD) times (1, 3, 5, 7 and 14 days). The following sequence of events was found in denervated myofibers of Cx43(fl/fl)Cx45(fl/fl) mice: 1) from day 3 PD, increase in sarcolemmal permeability, 2) from day 5 PD, increases of intracellular Ca2+ and Na+ signals as well as a significant increase in protein synthesis and degradation, yielding a negative protein balance and 3) from day 7 PD, a fall in myofibers cross-section area. All the above alterations were either absent or drastically reduced in denervated myofibers of Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice. Thus, the denervation-induced Cx HCs expression is an early event that precedes the electrochemical gradient dysregulation across the sarcolemma and critically contributes to the progression of skeletal muscle atrophy. Consequently, Cx HCs could be a therapeutic target to drastically prevent the denervation-induced atrophy of fast skeletal muscles. (C) 2016 Elsevier B.V. All rights reserved.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.1016/j.bbadis.2016.08.020
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleConnexin hemichannels explain the ionic imbalance and lead to atrophy in denervated skeletal muscles
dc.titleBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


Este ítem pertenece a la siguiente institución