Mostrar el registro sencillo del ítem
dc.contributor.author
Zheng, Jingjing
dc.contributor.author
Dooge, Holly C.
dc.contributor.author
Pérez Hernández, Marta
dc.contributor.author
Zhao, Yan-Ting
dc.contributor.author
Chen, Xi
dc.contributor.author
Hernandez, Jonathan J.
dc.contributor.author
Valdivia, Carmen R.
dc.contributor.author
Palomeque, Julieta
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Rothenberg, Eli
dc.contributor.author
Delmar, Mario
dc.contributor.author
Valdivia, Héctor H.
dc.contributor.author
Alvarado, Francisco J.
dc.date.available
2023-09-21T14:07:35Z
dc.date.issued
2022-06
dc.identifier.citation
Zheng, Jingjing; Dooge, Holly C.; Pérez Hernández, Marta; Zhao, Yan-Ting; Chen, Xi; et al.; Preserved cardiac performance and adrenergic response in a rabbit model with decreased ryanodine receptor 2 expression; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 167; 6-2022; 118-128
dc.identifier.issn
0022-2828
dc.identifier.uri
http://hdl.handle.net/11336/212478
dc.description.abstract
Ryanodine receptor 2 (RyR2) is an ion channel in the heart responsible for releasing into the cytosol most of the Ca2+ required for contraction. Proper regulation of RyR2 is critical, as highlighted by the association between channel dysfunction and cardiac arrhythmia. Lower RyR2 expression is also observed in some forms of heart disease; however, there is limited information on the impact of this change on excitation-contraction (e-c) coupling, Ca2+-dependent arrhythmias, and cardiac performance. We used a constitutive knock-out of RyR2 in rabbits (RyR2-KO) to assess the extent to which a stable decrease in RyR2 expression modulates Ca2+ handling in the heart. We found that homozygous knock-out of RyR2 in rabbits is embryonic lethal. Remarkably, heterozygotes (KO+/−) show ~50% loss of RyR2 protein without developing an overt phenotype at the intact animal and whole heart levels. Instead, we found that KO+/− myocytes show (1) remodeling of RyR2 clusters, favoring smaller groups in which channels are more densely arranged; (2) lower Ca2+ spark frequency and amplitude; (3) slower rate of Ca2+ release and mild but significant desynchronization of the Ca2+ transient; and (4) a significant decrease in the basal phosphorylation of S2031, likely due to increased association between RyR2 and PP2A. Our data show that RyR2 deficiency, although remarkable at the molecular and subcellular level, has only a modest impact on global Ca2+ release and is fully compensated at the whole-heart level. This highlights the redundancy of RyR2 protein expression and the plasticity of the e-c coupling apparatus.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Ltd - Elsevier Science Ltd
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CALCIUM
dc.subject
CARDIOMYOCYTE
dc.subject
E-C COUPLING
dc.subject
RYANODINE RECEPTOR
dc.subject
RYR2
dc.subject.classification
Fisiología
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Medicina Básica
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Preserved cardiac performance and adrenergic response in a rabbit model with decreased ryanodine receptor 2 expression
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-07-06T21:42:11Z
dc.journal.volume
167
dc.journal.pagination
118-128
dc.journal.pais
Estados Unidos
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.description.fil
Fil: Zheng, Jingjing. Sun Yat-sen University; China. University of Wisconsin; Estados Unidos
dc.description.fil
Fil: Dooge, Holly C.. University of Wisconsin; Estados Unidos
dc.description.fil
Fil: Pérez Hernández, Marta. University of New York; Estados Unidos
dc.description.fil
Fil: Zhao, Yan-Ting. University Of Michigan; Estados Unidos
dc.description.fil
Fil: Chen, Xi. University Of Michigan; Estados Unidos
dc.description.fil
Fil: Hernandez, Jonathan J.. University of Wisconsin; Estados Unidos
dc.description.fil
Fil: Valdivia, Carmen R.. University of Wisconsin; Estados Unidos
dc.description.fil
Fil: Palomeque, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
dc.description.fil
Fil: Rothenberg, Eli. University of New York; Estados Unidos
dc.description.fil
Fil: Delmar, Mario. University of New York; Estados Unidos
dc.description.fil
Fil: Valdivia, Héctor H.. University of Wisconsin; Estados Unidos
dc.description.fil
Fil: Alvarado, Francisco J.. University of Wisconsin; Estados Unidos
dc.journal.title
Journal of Molecular and Cellular Cardiology
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S002228282200061X
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.yjmcc.2022.04.004
Archivos asociados