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dc.contributor.authorGaeta, Stephen A.
dc.contributor.authorBub, Gil
dc.contributor.authorAbbott, Geoffrey W.
dc.contributor.authorChristini, David J.
dc.date.accessioned2024-11-15T15:43:18Z
dc.date.available2024-11-15T15:43:18Z
dc.date.issued2009-08-14
dc.identifier.citationGaeta SA, Bub G, Abbott GW, Christini DJ. Dynamical mechanism for subcellular alternans in cardiac myocytes. Circ Res. 2009 Aug 14;105(4):335-42. doi: 10.1161/CIRCRESAHA.109.197590. Epub 2009 Jul 23. PMID: 19628792; PMCID: PMC2740370.en_US
dc.identifier.issn0009-7330
dc.identifier.eissn1524-4571
dc.identifier.doi10.1161/circresaha.109.197590
dc.identifier.pmid19628792
dc.identifier.pii10.1161/CIRCRESAHA.109.197590
dc.identifier.urihttp://hdl.handle.net/20.500.12648/15819
dc.description.abstractRationale: Cardiac repolarization alternans is an arrhythmogenic rhythm disturbance, manifested in individual myocytes as a beat-to-beat alternation of action potential durations and intracellular calcium transient magnitudes. Recent experimental studies have reported "subcellular alternans," in which distinct regions of an individual cell are seen to have counterphase calcium alternations, but the mechanism by which this occurs is not well understood. Although previous theoretical work has proposed a possible dynamical mechanism for subcellular alternans formation, no direct evidence for this mechanism has been reported in vitro. Rather, experimental studies have generally invoked fixed subcellular heterogeneities in calcium-cycling characteristics as the mechanism of subcellular alternans formation. Objective: In this study, we have generalized the previously proposed dynamical mechanism to predict a simple pacing algorithm by which subcellular alternans can be induced in isolated cardiac myocytes in the presence or absence of fixed subcellular heterogeneity. We aimed to verify this hypothesis using computational modeling and to confirm it experimentally in isolated cardiac myocytes. Furthermore, we hypothesized that this dynamical mechanism may account for previous reports of subcellular alternans seen in statically paced, intact tissue. Methods and results: Using a physiologically realistic computational model of a cardiac myocyte, we show that our predicted pacing algorithm induces subcellular alternans in a manner consistent with theoretical predictions. We then use a combination of real-time electrophysiology and fluorescent calcium imaging to implement this protocol experimentally and show that it robustly induces subcellular alternans in isolated guinea pig ventricular myocytes. Finally, we use computational modeling to demonstrate that subcellular alternans can indeed be dynamically induced during static pacing of 1D fibers of myocytes during tissue-level spatially discordant alternans. Conclusion: Here we provide the first direct experimental evidence that subcellular alternans can be dynamically induced in cardiac myocytes. This proposed mechanism may contribute to subcellular alternans formation in the intact heart.en_US
dc.language.isoenen_US
dc.publisherOvid Technologies (Wolters Kluwer Health)en_US
dc.relation.urlhttps://www.ahajournals.org/doi/10.1161/CIRCRESAHA.109.197590en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleDynamical Mechanism for Subcellular Alternans in Cardiac Myocytesen_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleCirculation Researchen_US
dc.source.volume105
dc.source.issue4
dc.source.beginpage335
dc.source.endpage342
dc.description.versionVoRen_US
refterms.dateFOA2024-11-15T15:43:20Z
dc.description.institutionSUNY Downstateen_US
dc.description.departmentPhysiology and Pharmacologyen_US
dc.description.degreelevelN/Aen_US
dc.identifier.issue4en_US


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Attribution-NonCommercial-NoDerivatives 4.0 International
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