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dc.contributor.authorHiess, Florian
dc.contributor.authorVallmitjana Lees, Alexander
dc.contributor.authorWang, Ruiwu
dc.contributor.authorCheng, Hongqiang
dc.contributor.authorter Keurs, Henk
dc.contributor.authorChen, Ju
dc.contributor.authorHove Madsen, Leif
dc.contributor.authorBenítez Iglesias, Raúl
dc.contributor.authorChen, S. R. Wayne
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial
dc.date.accessioned2015-11-20T09:29:24Z
dc.date.available2016-11-22T01:30:44Z
dc.date.issued2015-08-14
dc.identifier.citationHiess, F., Vallmitjana, A., Wang, R., Cheng, H., ter Keurs, H., Chen, J., Hove-Madsen, L., Benitez, R., Chen, S. Distribution and function of cardiac ryanodine receptor clusters in live ventricular myocytes. "Journal of biological chemistry", 14 Agost 2015, vol. 290, núm. 33, p. 20477-20487.
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/2117/79512
dc.description.abstractThe cardiac Ca2+ release channel (ryanodine receptor, RyR2) plays an essential role in excitation-contraction coupling in cardiac muscle cells. Effective and stable excitation-contraction coupling critically depends not only on the expression of RyR2, but also on its distribution. Despite its importance, little is known about the distribution and organization of RyR2 in living cells. To study the distribution of RyR2 in living cardiomyocytes, we generated a knock-in mouse model expressing a GFP-tagged RyR2 (GFP-RyR2). Confocal imaging of live ventricular myocytes isolated from the GFP-RyR2 mouse heart revealed clusters of GFP-RyR2 organized in rows with a striated pattern. Similar organization of GFP-RyR2 clusters was observed in fixed ventricular myocytes. Immunofluorescence staining with the anti-alpha-actinin antibody (a z-line marker) showed that nearly all GFP-RyR2 clusters were localized in the z-line zone. There were small regions with dislocated GFP-RyR2 clusters. Interestingly, these same regions also displayed dislocated z-lines. Staining with di-8-ANEPPS revealed that nearly all GFP-RyR2 clusters were co-localized with transverse but not longitudinal tubules, whereas staining with MitoTracker Red showed that GFP-RyR2 clusters were not co-localized with mitochondria in live ventricular myocytes. We also found GFP-RyR2 clusters interspersed between z-lines only at the periphery of live ventricular myocytes. Simultaneous detection of GFP-RyR2 clusters and Ca2+ sparks showed that Ca2+ sparks originated exclusively from RyR2 clusters. Ca2+ sparks from RyR2 clusters induced no detectable changes in mitochondrial Ca2+ level. These results reveal, for the first time, the distribution of RyR2 clusters and its functional correlation in living ventricular myocytes.
dc.format.extent11 p.
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Enginyeria biomèdica::Electrònica biomèdica::Electrònica en cardiologia
dc.subject.lcshMedical electronics
dc.subject.otherRAT-HEART CELLS
dc.subject.otherCA2+ RELEASE SITES
dc.subject.otherCALCIUM TRANSIENTS
dc.subject.other3-DIMENSIONAL DISTRIBUTION
dc.subject.otherMITOCHONDRIAL CALCIUM
dc.subject.otherCONFOCAL MICROSCOPY
dc.subject.otherLOCAL-CONTROL
dc.subject.otherMUSCLE
dc.subject.otherSPARKS
dc.subject.otherCHANNEL
dc.titleDistribution and function of cardiac ryanodine receptor clusters in live ventricular myocytes
dc.typeArticle
dc.subject.lemacCardiologia
dc.contributor.groupUniversitat Politècnica de Catalunya. SISBIO - Senyals i Sistemes Biomèdics
dc.identifier.doi10.1074/jbc.M115.650531
dc.rights.accessOpen Access
local.identifier.drac16870220
dc.description.versionPostprint (author's final draft)
local.citation.authorHiess, F.; Vallmitjana, A.; Wang, R.; Cheng, H.; ter Keurs, H.; Chen, J.; Hove-Madsen, L.; Benitez, R.; Chen, S.
local.citation.publicationNameJournal of biological chemistry
local.citation.volume290
local.citation.number33
local.citation.startingPage20477
local.citation.endingPage20487


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