Document Detail


Altered dose response to beta-agonists in SERCA1a-expressing hearts ex vivo and in vivo.
MedLine Citation:
PMID:  12181124     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study we evaluated the contractile characteristics of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)1a-expressing hearts ex vivo and in vivo and in particular their response to beta-adrenergic stimulation. Analysis of isolated, work-performing hearts revealed that transgenic (TG) hearts develop much higher maximal rates of contraction and relaxation than wild-type (WT) hearts. Addition of isoproterenol only moderately increased the maximal rate of relaxation (+20%) but did not increase contractility or decrease relaxation time in TG hearts. Perfusion with varied buffer Ca(2+) concentrations indicated an altered dose response to Ca(2+). In vivo TG hearts displayed fairly higher maximal rates of contraction (+ 25%) but unchanged relaxation parameters and a blunted but significant response to dobutamine. Our study also shows that the phospholamban (PLB) level was decreased (-40%) and its phosphorylation status modified in TG hearts. This study clearly demonstrates that increases in SERCA protein level alter the beta-adrenergic response and affect the phosphorylation of PLB. Interestingly, the overall cardiac function in the live animal is only slightly enhanced, suggesting that (neuro)hormonal regulations may play an important role in controlling in vivo heart function.
Authors:
Sabine Huke; Vikram Prasad; Michelle L Nieman; Kalpana J Nattamai; Ingrid L Grupp; John N Lorenz; Muthu Periasamy
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  283     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-15     Completed Date:  2002-09-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H958-65     Citation Subset:  IM    
Affiliation:
Department of Physiology and Cell Biology, Ohio State University College of Medicine and Public Health, Columbus 43210, Ohio, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Agonists / pharmacology*
Animals
Calcium / pharmacology
Calcium-Binding Proteins / metabolism
Calcium-Transporting ATPases / genetics,  metabolism*
Dobutamine / pharmacology
Dose-Response Relationship, Drug
Female
Isoproterenol / pharmacology*
Male
Mice
Mice, Transgenic
Myocardial Contraction / drug effects*,  physiology
Myocardium / metabolism*
Phosphorylation
Receptors, Adrenergic, beta / metabolism
Sarcoplasmic Reticulum / enzymology
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Grant Support
ID/Acronym/Agency:
HL-64140-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Calcium-Binding Proteins; 0/Receptors, Adrenergic, beta; 0/phospholamban; 34368-04-2/Dobutamine; 7440-70-2/Calcium; 7683-59-2/Isoproterenol; EC 3.6.1.8/Calcium-Transporting ATPases; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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