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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2003-6-9
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pubmed:abstractText |
Changes in calcium (Ca2+) regulation contribute to loss of contractile function in dilated cardiomyopathy. Clinical treatment using beta-adrenergic receptor antagonists (beta-blockers) slows deterioration of cardiac function in end-stage heart failure patients; however, the effects of beta-blocker treatment on Ca2+ dynamics in the failing heart are unknown. To address this issue, tropomodulin-overexpressing transgenic (TOT) mice, which suffer from dilated cardiomyopathy, were treated with a nonselective beta-receptor blocker (5 mg. kg-1. day-1 propranolol) for 2 wk. Ca2+ dynamics in isolated cardiomyocytes of TOT mice significantly improved after treatment compared with untreated TOT mice. Frequency-dependent diastolic and Ca2+ transient amplitudes were returned to normal in propranolol-treated TOT mice and but not in untreated TOT mice. Ca2+ kinetic measurements of time to peak and time decay of the caffeine-induced Ca2+ transient to 50% relaxation were also normalized. Immunoblot analysis of untreated TOT heart samples showed a 3.6-fold reduction of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), whereas Na+/Ca2+ exchanger (NCX) concentrations were increased 2.6-fold relative to nontransgenic samples. Propranolol treatment of TOT mice reversed the alterations in SERCA and NCX protein levels but not potassium channels. Although restoration of Ca2+ dynamics occurred within 2 wk of beta-blockade treatment, evidence of functional improvement in cardiac contractility assessed by echocardiography took 10 wk to materialize. These results demonstrate that beta-adrenergic blockade restores Ca2+ dynamics and normalizes expression of Ca2+-handling proteins, eventually leading to improved hemodynamic function in cardiomyopathic hearts.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluo-3,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Propranolol,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine,
http://linkedlifedata.com/resource/pubmed/chemical/Sarcoplasmic Reticulum...,
http://linkedlifedata.com/resource/pubmed/chemical/Tlx2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tmod1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tropomodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Xanthenes
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0363-6135
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pubmed:author |
pubmed-author:BenkuskyNancyN,
pubmed-author:FisetCelineC,
pubmed-author:GlascockBettyB,
pubmed-author:HondaRitsuR,
pubmed-author:LalliM JaneMJ,
pubmed-author:PeriasamyMuthuM,
pubmed-author:PlankDavid MDM,
pubmed-author:SussmanMark AMA,
pubmed-author:ValdiviaHector HHH,
pubmed-author:WittSandraS,
pubmed-author:YataniAtsukoA
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pubmed:issnType |
Print
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H305-15
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12649072-Adrenergic beta-Antagonists,
pubmed-meshheading:12649072-Aniline Compounds,
pubmed-meshheading:12649072-Animals,
pubmed-meshheading:12649072-Blotting, Western,
pubmed-meshheading:12649072-Calcium,
pubmed-meshheading:12649072-Calcium Signaling,
pubmed-meshheading:12649072-Calcium-Transporting ATPases,
pubmed-meshheading:12649072-Carrier Proteins,
pubmed-meshheading:12649072-Electrophysiology,
pubmed-meshheading:12649072-Fluorescent Dyes,
pubmed-meshheading:12649072-Heart Failure,
pubmed-meshheading:12649072-Homeodomain Proteins,
pubmed-meshheading:12649072-Membrane Potentials,
pubmed-meshheading:12649072-Mice,
pubmed-meshheading:12649072-Mice, Transgenic,
pubmed-meshheading:12649072-Microfilament Proteins,
pubmed-meshheading:12649072-Muscle Cells,
pubmed-meshheading:12649072-Myocardial Contraction,
pubmed-meshheading:12649072-Myocardium,
pubmed-meshheading:12649072-Nuclease Protection Assays,
pubmed-meshheading:12649072-Patch-Clamp Techniques,
pubmed-meshheading:12649072-Propranolol,
pubmed-meshheading:12649072-Ryanodine,
pubmed-meshheading:12649072-Sarcoplasmic Reticulum Calcium-Transporting ATPases,
pubmed-meshheading:12649072-Tropomodulin,
pubmed-meshheading:12649072-Ventricular Remodeling,
pubmed-meshheading:12649072-Xanthenes
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pubmed:year |
2003
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pubmed:articleTitle |
Calcium dynamics in the failing heart: restoration by beta-adrenergic receptor blockade.
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pubmed:affiliation |
Divisions of Molecular Cardiovascular Biology, The Children's Hospital and Research Foundation, Cincinnati, OH 45229, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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