Cardiovascular Research

Cardiovascular Research 2003 57(2):505-514; doi:10.1016/S0008-6363(02)00662-4
© 2003 by European Society of Cardiology

This Article Full Text FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by van der Velden, J Articles by Stienen, G.J.M Search for Related Content PubMed PubMed Citation Articles by van der Velden, J Articles by Stienen, G.J.M Social Bookmarking          What's this?

Copyright © 2003, European Society of Cardiology

The effect of myosin light chain 2 dephosphorylation on Ca²⁺-sensitivity of force is enhanced in failing human hearts

J van der Velden^a,*, Z Papp^b, N.M Boontje^a, R Zaremba^a, J.W de Jong^c, P.M.L Janssen^d, G Hasenfuss^d and G.J.M Stienen^a

^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 Cardiology and Pneumology, Georg-August-University Goettingen, Goettingen, Germany

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

Objective: Phosphorylation of the myosin light chain 2 (MLC-2) isoform expressed as a percentage of total MLC-2 was decreased in failing (21.1±2.0%) compared to donor (31.9±4.8%) hearts. To assess the functional implications of this change, we compared the effects of MLC-2 dephosphorylation on force development in failing and non-failing (donor) human hearts. Methods: Cooperative effects in isometric force and rate of force redevelopment (K_tr) were studied in single Triton-skinned human cardiomyocytes at various [Ca²⁺] before and after protein phosphatase-1 (PP-1) incubation. Results: Maximum force and K_tr values did not differ between failing and donor hearts, but Ca²⁺-sensitivity of force (pCa₅₀) was significantly higher in failing myocardium (pCa₅₀=0.17). K_tr decreased with decreasing [Ca²⁺], although this decrease was less in failing than in donor hearts. Incubation of the myocytes with PP-1 (0.5 U/ml; 60 min) decreased pCa₅₀ to a larger extent in failing (0.20 pCa units) than in donor cardiomyocytes (0.10 pCa units). A decrease in absolute K_tr values was found after PP-1 in failing and donor myocytes, while the shape of the K_tr–Ca²⁺ relationships remained unaltered. Conclusions: Surprisingly, the contractile response to MLC-2 dephosphorylation is enhanced in failing hearts, despite the reduced level of basal MLC-2 phosphorylation. The enhanced response to MLC-2 dephosphorylation in failing myocytes might result from differences in basal phosphorylation of other thin and thick filament proteins between donor and failing hearts. Regulation of Ca²⁺-sensitivity via MLC-2 phosphorylation may be a potential compensatory mechanism to reverse the detrimental effects of increased Ca²⁺-sensitivity and impaired Ca²⁺-handling on diastolic function in human heart failure.

KEYWORDS Cardiomyopathy; Contractile apparatus; Contractile function; Myocytes; Signal transduction

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

This article has been cited by other articles:

				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]

				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]

				B. A. Colson, T. Bekyarova, M. R. Locher, D. P. Fitzsimons, T. C. Irving, and R. L. Moss Protein Kinase A-Mediated Phosphorylation of cMyBP-C Increases Proximity of Myosin Heads to Actin in Resting Myocardium Circ. Res., August 1, 2008; 103(3): 244 - 251. [Abstract] [Full Text] [PDF]

				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]

				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]

				L. M. Hanft, F. S. Korte, and K. S. McDonald Cardiac function and modulation of sarcomeric function by length Cardiovasc Res, March 1, 2008; 77(4): 627 - 636. [Abstract] [Full Text] [PDF]

				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]

				K. Brixius, R. Lu, B. Boelck, S. Grafweg, F. Hoyer, C. Pott, U. Mehlhorn, W. Bloch, and R. H. G. Schwinger Chronic Treatment with Carvedilol Improves Ca2+-Dependent ATP Consumption in Triton X-Skinned Fiber Preparations of Human Myocardium J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 222 - 227. [Abstract] [Full Text] [PDF]

				I. F. Edes, D. Czuriga, G. Csanyi, S. Chlopicki, F. A. Recchia, A. Borbely, Z. Galajda, I. Edes, J. van der Velden, G. J. M. Stienen, et al. Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R20 - R29. [Abstract] [Full Text] [PDF]

				M. C. de Waard, J. van der Velden, V. Bito, S. Ozdemir, L. Biesmans, N. M. Boontje, D. H.W. Dekkers, K. Schoonderwoerd, H. C.H. Schuurbiers, R. d. Crom, et al. Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction Circ. Res., April 13, 2007; 100(7): 1079 - 1088. [Abstract] [Full Text] [PDF]

				A. Neulen, N. Blaudeck, S. Zittrich, D. Metzler, G. Pfitzer, and R. Stehle Mn2+-dependent protein phosphatase 1 enhances protein kinase A-induced Ca2+ desensitisation in skinned murine myocardium Cardiovasc Res, April 1, 2007; 74(1): 124 - 132. [Abstract] [Full Text] [PDF]

				J. E. Stelzer, J. R. Patel, and R. L. Moss Acceleration of Stretch Activation in Murine Myocardium due to Phosphorylation of Myosin Regulatory Light Chain J. Gen. Physiol., August 28, 2006; 128(3): 261 - 272. [Abstract] [Full Text] [PDF]

				F. C. Chen and O. Ogut Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin Am J Physiol Cell Physiol, March 1, 2006; 290(3): C719 - C727. [Abstract] [Full Text] [PDF]

				J. van der Velden, N. A. Narolska, R. R. Lamberts, N. M. Boontje, A. Borbely, R. Zaremba, J. G.F. Bronzwaer, Z. Papp, K. Jaquet, W. J. Paulus, et al. Functional effects of protein kinase C-mediated myofilament phosphorylation in human myocardium Cardiovasc Res, March 1, 2006; 69(4): 876 - 887. [Abstract] [Full Text] [PDF]

				S. E. Kirschner, E. Becker, M. Antognozzi, H.-P. Kubis, A. Francino, F. Navarro-Lopez, N. Bit-Avragim, A. Perrot, M. M. Mirrakhimov, K.-J. Osterziel, et al. Hypertrophic cardiomyopathy-related {beta}-myosin mutations cause highly variable calcium sensitivity with functional imbalances among individual muscle cells Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1242 - H1251. [Abstract] [Full Text] [PDF]

				S. Sakthivel, N. L. Finley, P. R. Rosevear, J. N. Lorenz, J. Gulick, S. Kim, P. VanBuren, L. A. Martin, and J. Robbins In Vivo and in Vitro Analysis of Cardiac Troponin I Phosphorylation J. Biol. Chem., January 7, 2005; 280(1): 703 - 714. [Abstract] [Full Text] [PDF]

				N.A. Narolska, R.B. van Loon, N.M. Boontje, R. Zaremba, S. E. Penas, J. Russell, S.R. Spiegelenberg, M.A.J.M. Huybregts, F.C. Visser, J.W. de Jong, et al. Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue Cardiovasc Res, January 1, 2005; 65(1): 221 - 229. [Abstract] [Full Text] [PDF]

				Y. Pi, D. Zhang, K. R Kemnitz, H. Wang, and J. W Walker Protein kinase C and A sites on troponin I regulate myofilament Ca2+ sensitivity and ATPase activity in the mouse myocardium J. Physiol., November 1, 2003; 552(3): 845 - 857. [Abstract] [Full Text] [PDF]

Online ISSN 1755-3245 - Print ISSN 0008-6363

Copyright © 2009 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics