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Mitochondrial calcium increase induced by RyR1 and IP3R channel activation after membrane depolarization regulates skeletal muscle metabolism

Authordc.contributor.authorDíaz Vegas, Alexis 
Authordc.contributor.authorCórdova, A. 
Authordc.contributor.authorValladares, Denisse 
Authordc.contributor.authorLlanos Vidal, Paola 
Authordc.contributor.authorHidalgo, C. 
Authordc.contributor.authorGherardi, Gaia 
Authordc.contributor.authorStefani, Diego De 
Authordc.contributor.authorMammucari, Cristina 
Authordc.contributor.authorRizzuto, Rosario 
Authordc.contributor.authorContreras Ferrat, Ariel Eduardo 
Authordc.contributor.authorJaimovich Pérez, Enrique 
Admission datedc.date.accessioned2018-11-08T20:30:43Z
Available datedc.date.available2018-11-08T20:30:43Z
Publication datedc.date.issued2018-06
Cita de ítemdc.identifier.citationFrontiers in Physiology Volumen: 9 Número de artículo: 791es_ES
Identifierdc.identifier.other10.3389/fphys.2018.00791
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/152524
Abstractdc.description.abstractAim: We hypothesize that both type-1 ryanodine receptor (RyR1) and IP3-receptor (IP3R) calcium channels are necessary for the mitochondrial Ca2+ increase caused by membrane depolarization induced by potassium (or by electrical stimulation) of single skeletal muscle fibers; this calcium increase would couple muscle fiber excitation to an increase in metabolic output from mitochondria (excitation-metabolism coupling). Methods: Mitochondria matrix and cytoplasmic Ca2+ levels were evaluated in fibers isolated from flexor digitorium brevis muscle using plasmids for the expression of a mitochondrial Ca2+ sensor (CEPIA3mt) or a cytoplasmic Ca2+ sensor (RCaMP). The role of intracellular Ca2+ channels was evaluated using both specific pharmacological inhibitors (xestospongin B for IP3R and Dantrolene for RyR1) and a genetic approach (shIP(3)R1-RFP). O-2 consumption was detected using Seahorse Extracellular Flux Analyzer. Results: In isolated muscle fibers cell membrane depolarization increased both cytoplasmic and mitochondrial Ca2+ levels. Mitochondrial C-a2+ uptake required functional inositol IP3R and RyR1 channels. Inhibition of either channel decreased basal O-2 consumption rate but only RyR1 inhibition decreased ATP-linked O-2 consumption. Cell membrane depolarization-induced Ca2+ signals in sub-sarcolemmal mitochondria were accompanied by a reduction in mitochondrial membrane potential; Ca2+ signals propagated toward intermyofibrillar mitochondria, which displayed increased membrane potential. These results are compatible with slow, Ca2+-dependent propagation of mitochondrial membrane potential from the surface toward the center of the fiber. Conclusion: Ca2+-dependent changes in mitochondrial membrane potential have different kinetics in the surface vs. the center of the fiber; these differences are likely to play a critical role in the control of mitochondrial metabolism, both at rest and after membrane depolarization as part of an excitation-metabolism coupling process in skeletal muscle fibers.es_ES
Patrocinadordc.description.sponsorshipFONDECYT 1151293 AT 21150604 11150243 BNI-09-15-F 11130267es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherFrontiers Mediaes_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
Sourcedc.sourceFrontiers in Physiologyes_ES
Keywordsdc.subjectEnergy distributiones_ES
Keywordsdc.subjectInositol 1, 4, 5-trisphosphate receptores_ES
Keywordsdc.subjectMitochondria heterogeneityes_ES
Keywordsdc.subjectMitochondrial networkes_ES
Keywordsdc.subjectRyanodine receptorses_ES
Títulodc.titleMitochondrial calcium increase induced by RyR1 and IP3R channel activation after membrane depolarization regulates skeletal muscle metabolismes_ES
Document typedc.typeArtículo de revistaes_ES
Catalogueruchile.catalogadorrgfes_ES
Indexationuchile.indexArtículo de publicación ISIes_ES


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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile