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dc.contributor.authorLimbu, Sarita
dc.contributor.authorProsser, Benjamin L
dc.contributor.authorLederer, William J
dc.contributor.authorWard, Christopher W
dc.contributor.authorJafri, Mohsin S
dc.date.accessioned2021-06-09T13:30:42Z
dc.date.available2021-06-09T13:30:42Z
dc.date.issued2021-05-13
dc.identifier.urihttp://hdl.handle.net/10713/15950
dc.description.abstractThe stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca2+ release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient.en_US
dc.description.urihttps://doi.org/10.3390/cells10051189en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCellsen_US
dc.subjectblebbistatinen_US
dc.subjectcalciumen_US
dc.subjectcomputational modelen_US
dc.subjecthearten_US
dc.subjectreactive oxygen speciesen_US
dc.titleX-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponinen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cells10051189
dc.identifier.pmid34068012
dc.source.volume10
dc.source.issue5
dc.source.countryUnited States
dc.source.countrySwitzerland


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