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dc.contributor.authorRubart, Michaelen_US
dc.contributor.authorTao, Wenen_US
dc.contributor.authorLu, Xiao-Longen_US
dc.contributor.authorConway, Simon J.en_US
dc.contributor.authorReuter, Sean P.en_US
dc.contributor.authorLin, Shien-Fongen_US
dc.contributor.authorSoonpaa, Mark H.en_US
dc.date.accessioned2018-08-21T05:53:24Z-
dc.date.available2018-08-21T05:53:24Z-
dc.date.issued2018-03-01en_US
dc.identifier.issn0008-6363en_US
dc.identifier.urihttp://dx.doi.org/10.1093/cvr/cvx163en_US
dc.identifier.urihttp://hdl.handle.net/11536/144641-
dc.description.abstractRecent studies have demonstrated electrotonic coupling between scar tissue and the surrounding myocardium in cryoinjured hearts. However, the electrical dynamics occurring at the myocyte-nonmyocyte interface in the fibrotic heart remain undefined. Here, we sought to develop an assay to interrogate the nonmyocyte cell type contributing to heterocellular coupling and to characterize, on a cellular scale, its voltage response in the infarct border zone of living hearts. We used two-photon laser scanning microscopy in conjunction with a voltage-sensitive dye to record transmembrane voltage changes simultaneously from cardiomyocytes and adjoined nonmyocytes in Langendorff-perfused mouse hearts with healing myocardial infarction. Transgenic mice with cardiomyocyte-restricted expression of a green fluorescent reporter protein underwent permanent coronary artery ligation and their hearts were subjected to voltage imaging 7-10 days later. Reporter-negative cells, i.e. nonmyocytes, in the infarct border zone exhibited depolarizing transients at a 1:1 coupling ratio with action potentials recorded simultaneously from adjacent, reporter-positive ventricular myocytes. The electrotonic responses in the nonmyocytes exhibited slower rates of de- and repolarization compared to the action potential waveform of juxtaposed myocytes. Voltage imaging in infarcted hearts expressing a fluorescent reporter specifically in myofibroblasts revealed that the latter were electrically coupled to border zone myocytes. Their voltage transient properties were indistinguishable from those of nonmyocytes in hearts with cardiomyocyte-restricted reporter expression. The density of connexin43 expression at myofibroblast-cardiomyocyte junctions was similar to 5% of that in the intercalated disc regions of paired ventricular myocytes in the remote, uninjured myocardium, whereas the ratio of connexin45 to connexin43 expression levels at heterocellular contacts was similar to 1%. Myofibroblasts contribute to the population of electrically coupled nonmyocytes in the infarct border zone. The slower kinetics of myofibroblast voltage responses may reflect low electrical conductivity across heterocellular junctions, in accordance with the paucity of connexin expression at myofibroblast-cardiomyocyte contacts.en_US
dc.language.isoen_USen_US
dc.subjectCardiac fibroblasten_US
dc.subjectElectrical couplingen_US
dc.subjectTwo-photon fluorescence microscopyen_US
dc.subjectMyocardial infarctionen_US
dc.subjectPeriostinen_US
dc.titleElectrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse hearten_US
dc.typeArticleen_US
dc.identifier.doi10.1093/cvr/cvx163en_US
dc.identifier.journalCARDIOVASCULAR RESEARCHen_US
dc.citation.volume114en_US
dc.citation.spage389en_US
dc.citation.epage400en_US
dc.contributor.department分子醫學與生物工程研究所zh_TW
dc.contributor.departmentInstitute of Molecular Medicine and Bioengineeringen_US
dc.identifier.wosnumberWOS:000426815000012en_US
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