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Cited by 147Cardiomyopathy and Myosin StudiesCardiovascular Function and Risk FactorsCardiac electrophysiology and arrhythmias

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

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

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VANDERVELDEN, J, PAPP, Z, BOONTJE, N, ZAREMBA, R, DEJONG, J, JANSSEN, P, HASENFUSS, G, STIENEN, G·2003·Cardiovascular Research
DOI 10.1016/s0008-6363(02)00662-4
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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 (K(tr)) were studied in single Triton-skinned human cardiomyocytes at various [Ca(2+)] 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 Ca(2+)-sensitivity of force (pCa(50)) was significantly higher in failing myocardium (Deltap Ca(50)=0.17). K(tr) decreased with decreasing [Ca(2+)], 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)-Ca(2+) 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 Ca(2+)-sensitivity via MLC-2 phosphorylation may be a potential compensatory mechanism to reverse the detrimental effects of increased Ca(2+)-sensitivity and impaired Ca(2+)-handling on diastolic function in human heart failure.

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Metadata

Authors
VANDERVELDEN, J., PAPP, Z., BOONTJE, N., ZAREMBA, R., DEJONG, J., JANSSEN, P., HASENFUSS, G., & STIENEN, G.
Affiliations
  • University of Debrecen (HU)
  • Amsterdam Cardiovascular Sciences (NL)
  • Vrije Universiteit Amsterdam (NL)
  • Erasmus University Rotterdam (NL)
  • University of Göttingen (DE)
ORCID
Venue
Cardiovascular Research
Publisher
Oxford University Press (OUP)
Published
2003-02-01
Volume
57
Issue
2
Pages
505-514
ISSN
0008-6363 (ISSN-L)
DOI
10.1016/s0008-6363(02)00662-4
OpenAlex
W2070092583
Cited by
147
References
34
Citations by year
2026: 6 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 1 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 9 · 2012: 6
FWCI
5.05
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Cardiovascular Research (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
  • GRO (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
myosin light chain 2, calcium sensitivity of contraction, heart failure, protein phosphatase 1, human cardiomyocytes, thin filament regulation, compensatory mechanisms, diastolic function, calcium handling
MeSH terms
Adult, Calcium, Cells, Cultured, Female, Heart Failure, Humans, Male, Middle Aged, Myocardial Contraction, Phosphoprotein Phosphatases, Phosphorylation, Electrophoresis, Gel, Two-Dimensional, Myosin Light Chains, Cardiac Myosins, Myocytes, Cardiac, Protein Phosphatase 1

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