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dc.contributor.authorChan, Yi-Hsinen_US
dc.contributor.authorTsai, Wei-Chungen_US
dc.contributor.authorSong, Zhenen_US
dc.contributor.authorKo, Christopher Y.en_US
dc.contributor.authorQu, Zhilinen_US
dc.contributor.authorWeiss, James N.en_US
dc.contributor.authorLin, Shien-Fongen_US
dc.contributor.authorChen, Peng-Shengen_US
dc.contributor.authorJones, Larry R.en_US
dc.contributor.authorChen, Zhenhuien_US
dc.date.accessioned2015-07-21T08:28:54Z-
dc.date.available2015-07-21T08:28:54Z-
dc.date.issued2015-03-01en_US
dc.identifier.issn0022-2828en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.yjmcc.2014.12.024en_US
dc.identifier.urihttp://hdl.handle.net/11536/124850-
dc.description.abstractPhospholamban (PLB) inhibits the activity of cardiac sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). Phosphorylation of PLB during sympathetic activation reverses SERCA2a inhibition, increasing SR Ca2+ uptake. However, sympathetic activation also modulates multiple other intracellular targets in ventricular myocytes (VMs), making it impossible to determine the specific effects of the reversal of PLB inhibition on the spontaneous SR Ca2+ release. Therefore, it remains unclear how PLB regulates rhythmic activity in VMs. Here, we used the Fab fragment of 2D12, a monoclonal anti-PLB antibody, to test how acute reversal of PLB inhibition affects the spontaneous SR Ca2+ release in normal VMs. Ca2+ sparks and spontaneous Ca2+ waves (SCWs) were recorded in the line-scan mode of confocal microscopy using the Ca2+ fluorescent dye Fluo-4 in isolated permeabilized mouse VMs. Fab, which reverses PLB inhibition, significantly increased the frequency, amplitude, and spatial/temporal spread of Ca2+ sparks in VMs exposed to 50 nM free [Ca2+]. At physiological diastolic free [Ca2+] (100-200 nM), Fab facilitated the formation of whole-cell propagating SCWs. At higher free [Ca2+], Fab increased the frequency and velocity, but decreased the decay time of the SCWs. cAMP had little additional effect on the frequency or morphology of Ca2+ sparks or SCWs after Fab addition. These findings were complemented by computer simulations. In conclusion, acute reversal of PLB inhibition alone significantly increased the spontaneous SR Ca2+ release, leading to the facilitation and organization of whole-cell propagating SCWs in normal VMs. PLB thus plays a key role in subcellular Ca2+ dynamics and rhythmic activity of VMs. (C) 2015 Elsevier Ltd. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectCalciumen_US
dc.subjectSarcoplasmic reticulumen_US
dc.subjectPhospholambanen_US
dc.subjectSpontaneousen_US
dc.subjectcalcium wavesen_US
dc.titleAcute reversal of phospholamban inhibition facilitates the rhythmic whole-cell propagating calcium waves in isolated ventricular myocytesen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.yjmcc.2014.12.024en_US
dc.identifier.journalJOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGYen_US
dc.citation.volume80en_US
dc.citation.spage126en_US
dc.citation.epage135en_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:000355389800015en_US
dc.citation.woscount0en_US
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