Skip Navigation

Cardiovascular Research 2003 57(1):37-47; doi:10.1016/S0008-6363(02)00606-5
© 2003 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by van der Velden, J
Right arrow Articles by Stienen, G.J.M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van der Velden, J
Right arrow Articles by Stienen, G.J.M
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2003, European Society of Cardiology

Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins

J van der Veldena,*, Z Pappb, R Zarembaa, N.M Boontjea, J.W de Jongc, V.J Owend, P.B.J Burtond, P Goldmanne, K Jaquete and G.J.M Stienena

aLaboratory for Physiology, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
bUDMHSC Department of Cardiology, Debrecen, Hungary
cThorax Center, Erasmus University, Rotterdam, The Netherlands
dDepartment of Cardiac Surgery, National Heart and Lung Institute at the Imperial College School of Medicine, London, UK
eRuhr-Universität, Institut für Physiologische Chemie, Abteilung für Biochemie Supramolekularer Systeme, Bochum, Germany

* Corresponding author. Tel.: +31-20-444-8121; fax: +31-20-444-8255 j.van_der_velden.physiol{at}med.vu.nl

Objective: The alterations in contractile proteins underlying enhanced Ca2+-sensitivity of the contractile apparatus in end-stage failing human myocardium are still not resolved. In the present study an attempt was made to reveal to what extent protein alterations contribute to the increased Ca2+-responsiveness in human heart failure. Methods: Isometric force and its Ca2+-sensitivity were studied in single left ventricular myocytes from non-failing donor (n=6) and end-stage failing (n=10) hearts. To elucidate which protein alterations contribute to the increased Ca2+-responsiveness isoform composition and phosphorylation status of contractile proteins were analysed by one- and two-dimensional gel electrophoresis and Western immunoblotting. Results: Maximal tension did not differ between myocytes obtained from donor and failing hearts, while Ca2+-sensitivity of the contractile apparatus (pCa50) was significantly higher in failing myocardium ({Delta}pCa50=0.17). Protein analysis indicated that neither re-expression of atrial light chain 1 and fetal troponin T (TnT) nor degradation of myosin light chains and troponin I (TnI) are responsible for the observed increase in Ca2+-responsiveness. An inverse correlation was found between pCa50 and percentage of phosphorylated myosin light chain 2 (MLC-2), while phosphorylation of MLC-1 and TnT did not differ between donor and failing hearts. Incubation of myocytes with protein kinase A decreased Ca2+-sensitivity to a larger extent in failing ({Delta}pCa50=0.20) than in donor ({Delta}pCa50=0.03) myocytes, abolishing the difference in Ca2+-responsiveness. An increased percentage of dephosphorylated TnI was found in failing hearts, which significantly correlated with the enhanced Ca2+-responsiveness. Conclusions: The increased Ca2+-responsiveness of the contractile apparatus in end-stage failing human hearts cannot be explained by a shift in contractile protein isoforms, but results from the complex interplay between changes in the phosphorylation status of MLC-2 and TnI.

KEYWORDS Contractile function; Heart failure; Myocytes; Protein phosphorylation


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
Circ Heart FailHome page
D. J. Duncker, N. M. Boontje, D. Merkus, A. Versteilen, J. Krysiak, G. Mearini, A. El-Armouche, V. J. de Beer, J. M.J. Lamers, L. Carrier, et al.
Prevention of Myofilament Dysfunction by {beta}-Blocker Therapy in Postinfarct Remodeling
Circ Heart Fail, May 1, 2009; 2(3): 233 - 242.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
L. M. Hanft and K. S. McDonald
Sarcomere length dependence of power output is increased after PKA treatment in rat cardiac myocytes
Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1524 - H1531.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
A. Borbely, I. Falcao-Pires, L. van Heerebeek, N. Hamdani, I. Edes, C. Gavina, A. F. Leite-Moreira, J. G.F. Bronzwaer, Z. Papp, J. van der Velden, et al.
Hypophosphorylation of the Stiff N2B Titin Isoform Raises Cardiomyocyte Resting Tension in Failing Human Myocardium
Circ. Res., March 27, 2009; 104(6): 780 - 786.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. J. van Dijk, D. Dooijes, C. dos Remedios, M. Michels, J. M.J. Lamers, S. Winegrad, S. Schlossarek, L. Carrier, F. J. ten Cate, G. J.M. Stienen, et al.
Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy: Haploinsufficiency, Deranged Phosphorylation, and Cardiomyocyte Dysfunction
Circulation, March 24, 2009; 119(11): 1473 - 1483.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
S. B. Scruggs, A. C. Hinken, A. Thawornkaiwong, J. Robbins, L. A. Walker, P. P. de Tombe, D. L. Geenen, P. M. Buttrick, and R. J. Solaro
Ablation of Ventricular Myosin Regulatory Light Chain Phosphorylation in Mice Causes Cardiac Dysfunction in Situ and Affects Neighboring Myofilament Protein Phosphorylation
J. Biol. Chem., February 20, 2009; 284(8): 5097 - 5106.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
Y. A. Mou, C. Reboul, L. Andre, A. Lacampagne, and O. Cazorla
Late exercise training improves non-uniformity of transmural myocardial function in rats with ischaemic heart failure
Cardiovasc Res, February 15, 2009; 81(3): 555 - 564.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
A. M. Jacques, N. Briceno, A. E. Messer, C. E. Gallon, S. Jalilzadeh, E. Garcia, G. Kikonda-Kanda, J. Goddard, S. E. Harding, H. Watkins, et al.
The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy
Cardiovasc Res, August 1, 2008; 79(3): 481 - 491.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
N. Hamdani, V. Kooij, S. van Dijk, D. Merkus, W. J. Paulus, C. d. Remedios, D. J. Duncker, G. J.M. Stienen, and J. van der Velden
Sarcomeric dysfunction in heart failure
Cardiovasc Res, March 1, 2008; 77(4): 649 - 658.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
R. R. Lamberts, N. Hamdani, T. W. Soekhoe, N. M. Boontje, R. Zaremba, L. A. Walker, P. P. de Tombe, J. van der Velden, and G. J. M. Stienen
Frequency-dependent myofilament Ca2+ desensitization in failing rat myocardium
J. Physiol., July 15, 2007; 582(2): 695 - 709.
[Abstract] [Full Text] [PDF]


Home page
Eur J Heart FailHome page
M. Adamcova, M. Sterba, T. Simunek, A. Potacova, O. Popelova, and V. Gersl
Myocardial regulatory proteins and heart failure
Eur J Heart Fail, June 1, 2006; 8(4): 333 - 342.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
W. Schillinger and H. Kogler
Altered phosphorylation and Ca2+-sensitivity of myofilaments in human heart failure
Cardiovasc Res, January 1, 2003; 57(1): 5 - 7.
[Full Text] [PDF]



Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.