| Plasticity of Surface Structures and β2-Adrenergic Receptor Localization in Failing Ventricular Cardiomyocytes During Recovery from Heart Failure. | |
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MedLine Citation:
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PMID: 22456061 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: -Cardiomyocyte surface morphology and T-tubular structure are significantly disrupted in chronic heart failure with important functional sequelae, including redistribution of sarcolemmal beta2adrenergic receptors (β(2)AR) and localized secondary messenger signaling. Plasticity of these changes in the reverse remodeled failing ventricle is unknown. We used AAV9.SERCA2a gene therapy to rescue failing rat hearts, and measured z-groove index, T-tubule density and compartmentalized β(2)AR-mediated cAMP signals using a combined nanoscale scanning ion conductance microscopy-Förster resonance energy transfer technique. METHODS AND RESULTS: -Cardiomyocyte surface morphology, quantified by z-groove index and T-tubule density, was normalized in reverse remodeled hearts following SERCA2a gene therapy. Recovery of sarcolemmal microstructure correlated with functional β(2)AR redistribution back into the z-groove and T-tubular network, whereas minimal cAMP responses were initiated following local β(2)AR stimulation of crest membrane, as observed in failing cardiomyocytes. Improvement of β(2)AR localization was associated with recovery of βAR-stimulated contractile responses in rescued cardiomyocytes. Retubulation was associated with reduced spatial heterogeneity of electrically-stimulated calcium transients, and recovery of myocardial BIN-1 and TCAP protein expression, but not junctophilin-2. CONCLUSIONS: -In summary, abnormalities of sarcolemmal structure in heart failure show plasticity with reappearance of z-grooves and T-tubules in reverse remodeled hearts. Recovery of surface topology is necessary for normalization of β(2)AR location and signaling responses. |
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Authors:
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Alexander R Lyon; Viacheslav O Nikolaev; Michele Miragoli; Markus B Sikkel; Helen Paur; Ludovic Benard; Jean-Sebastien Hulot; Erik Kohlbrenner; Roger J Hajjar; Nicholas S Peters; Yuri E Korchev; Kenneth T Macleod; Sian E Harding; Julia Gorelik |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-28 |
Journal Detail:
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Title: Circulation. Heart failure Volume: - ISSN: 1941-3297 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101479941 Medline TA: Circ Heart Fail Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Imperial College and Royal Brompton Hospital, London, UK; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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