| Chronic coexistence of two troponin T isoforms in adult transgenic mouse cardiomyocytes decreased contractile kinetics and caused dilatative remodeling. | |
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MedLine Citation:
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PMID: 22538236 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Our previous in vivo and ex vivo studies suggested that coexistence of two or more troponin T (TnT) isoforms in adult cardiac muscle decreased cardiac function and efficiency (Huang QQ, Feng HZ, Liu J, Du J, Stull LB, Moravec CS, Huang X, Jin JP, Am J Physiol Cell Physiol 294: C213-C22, 2008; Feng HZ, Jin JP, Am J Physiol Heart Circ Physiol 299: H97-H105, 2010). Here we characterized Ca(2+)-regulated contractility of isolated adult cardiomyocytes from transgenic mice coexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT. Without the influence of extracellular matrix, coexistence of the two TnT isoforms resulted in lower shortening amplitude, slower shortening and relengthening velocities, and longer relengthening time. The level of resting cytosolic Ca(2+) was unchanged, but the peak Ca(2+) transient was lowered and the durations of Ca(2+) rising and decaying were longer in the transgenic mouse cardiomyocytes vs. the wild-type controls. Isoproterenol treatment diminished the differences in shortening amplitude and shortening and relengthening velocities, whereas the prolonged durations of relengthening and Ca(2+) transient in the transgenic cardiomyocytes remained. At rigor state, a result from depletion of Ca(2+), resting sarcomere length of the transgenic cardiomyocytes became shorter than that in wild-type cells. Inhibition of myosin motor diminished this effect of TnT function on cross bridges. The length but not width of transgenic cardiomyocytes was significantly increased compared with the wild-type controls, corresponding to longitudinal addition of sarcomeres and dilatative remodeling at the cellular level. These dominantly negative effects of normal fast TnT demonstrated that chronic coexistence of functionally distinct variants of TnT in adult cardiomyocytes reduces contractile performance with pathological consequences. |
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Authors:
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Zhi-Bin Yu; Hongguang Wei; J-P Jin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-04-25 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: 303 ISSN: 1522-1563 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-07-03 Completed Date: 2012-09-11 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: C24-32 Citation Subset: IM |
Affiliation:
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Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism Cells, Cultured Extracellular Matrix / physiology Female Isoproterenol / pharmacology Male Mice Mice, Inbred C57BL Mice, Transgenic Myocardial Contraction / physiology* Myocardium / metabolism Myocytes, Cardiac / metabolism* Protein Isoforms Troponin T / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AR-048816/AR/NIAMS NIH HHS; HL-078773/HL/NHLBI NIH HHS; HL-098945/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Protein Isoforms; 0/Troponin T; 7440-70-2/Calcium; 7683-59-2/Isoproterenol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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