The effect of myosin light chain 2 dephosphorylation on Ca2+-sensitivity of force is enhanced in failing human hearts
2003 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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The effect of myosin light chain 2 dephosphorylation on Ca2+-sensitivity of force is enhanced in failing human hearts
van der Velden, J.; Papp, Z.; Boontje, N. M.; Zaremba, R.; Jong, J. W. de; Janssen, P. M. L. & Hasenfuß, G. et al. (2003)
Cardiovascular Research, 57(2) art. PII S0008-6363(02)00662-4. DOI: https://doi.org/10.1016/S0008-6363(02)00662-4
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- Authors
- van der Velden, J.; Papp, Zoltan; Boontje, N. M.; Zaremba, R; Jong, J. W. de; Janssen, P. M. L.; Hasenfuß, Gerd ; Stienen, G. J. M.
- Abstract
- 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 (Kt,) 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, values did not differ between failing and donor hearts, but Ca2+-sensitivity of force (pCa(50)) was significantly higher in failing myocardium (DeltapCa(50)=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 pCa(50) 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. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
- Issue Date
- 2003
- Publisher
- Elsevier Science Bv
- Journal
- Cardiovascular Research
- ISSN
- 0008-6363