Enhanced capacity for CaMKII signaling mitigates calcium release related contractile fatigue with high intensity exercise

Martin Flück*, Colline Sanchez, Vincent Jacquemond, Christine Berthier, Marie Noëlle Giraud, Daniel Jacko, Käthe Bersiner, Sebastian Gehlert, Guus Baan, Richard T. Jaspers

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: We tested whether enhancing the capacity for calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling would delay fatigue of excitation-induced calcium release and improve contractile characteristics of skeletal muscle during fatiguing exercise. Methods: Fast and slow type muscle, gastrocnemius medialis (GM) and soleus (SOL), of rats and mouse interosseus (IO) muscle fibers, were transfected with pcDNA3-based plasmids for rat α and β CaMKII or empty controls. Levels of CaMKII, its T287-phosphorylation (pT287-CaMKII), and phosphorylation of components of calcium release and re-uptake, ryanodine receptor 1 (pS2843-RyR1) and phospholamban (pT17-PLN), were quantified biochemically. Sarcoplasmic calcium in transfected muscle fibers was monitored microscopically during trains of electrical excitation based on Fluo-4 FF fluorescence (n = 5–7). Effects of low- (n = 6) and high- (n = 8) intensity exercise on pT287-CaMKII and contractile characteristics were studied in situ. Results: Co-transfection with αCaMKII-pcDNA3/βCaMKII-pcDNA3 increased α and βCaMKII levels in SOL (+45.8 %, +250.5 %) and GM (+40.4 %, +89.9 %) muscle fibers compared to control transfection. High-intensity exercise increased pT287-βCaMKII and pS2843-RyR1 levels in SOL (+269 %, +151 %) and GM (+354 %, +119 %), but decreased pT287-αCaMKII and p17-PLN levels in GM compared to SOL (−76 % vs. +166 %; 0 % vs. +128 %). α/β CaMKII overexpression attenuated the decline of calcium release in muscle fibers with repeated excitation, and mitigated exercise-induced deterioration of rates in force production, and passive force, in a muscle-dependent manner, in correlation with pS2843-RyR1 and pT17-PLN levels (|r| > 0.7). Conclusion: Enhanced capacity for α/β CaMKII signaling improves fatigue-resistance of active and passive contractile muscle properties in association with RyR1- and PLN-related improvements in sarcoplasmic calcium release.

Original languageEnglish
Article number119610
Pages (from-to)1-13
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1871
Issue number2
Early online date31 Oct 2023
DOIs
Publication statusPublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Funding

The study was funded by the European Commission as a ERASMUS MUNDUS grant on “Signalling of muscle fibre recruitment via the calcium sensor CaMKII”. The funding organization did not influence the study design, the collection, analysis and interpretation of data, the writing of the report, and the decision to submit the article.

FundersFunder number
European Commission
Erasmus+

    Keywords

    • Contraction
    • Fatigue
    • Force
    • Phosphorylation
    • Ryanodine receptor
    • Velocity

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