Artículo
Preserved cardiac performance and adrenergic response in a rabbit model with decreased ryanodine receptor 2 expression
Zheng, Jingjing; Dooge, Holly C.; Pérez Hernández, Marta; Zhao, Yan-Ting; Chen, Xi; Hernandez, Jonathan J.; Valdivia, Carmen R.; Palomeque, Julieta
; Rothenberg, Eli; Delmar, Mario; Valdivia, Héctor H.; Alvarado, Francisco J.
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
06/2022
Editorial:
Academic Press Ltd - Elsevier Science Ltd
Revista:
Journal of Molecular and Cellular Cardiology
ISSN:
0022-2828
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
CALCIUM
,
CARDIOMYOCYTE
,
E-C COUPLING
,
RYANODINE RECEPTOR
,
RYR2
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Colecciones
Articulos(CIC)
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)
Citación
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
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