February 2, 2018Scientific ReportsOpen Access

Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca2+-dependent manner

Q: What is the clinical evidence from this study?

Population: Muscle contraction. Intervention: Recombinant N-terminal fragments of MyBP-C isoforms (ssC1C2, fsC1C2, C0C2) vs. Untreated control. Primary outcome: Thin filament sliding velocity and force production at varying Ca2+ levels.

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Key result

Cardiac MyBP-C activates thin filament sliding at low calcium but increases force at high calcium.

Population

Preclinical models: permeabilized rat papillary muscle fibers, mouse ventricular myosin and native thin…

Comparison

Recombinant N-terminal fragments of MyBP-C… vs Vehicle control, low Ca2+ control filaments, or…

Design

Preclinical

Authors

BLBrian L. LinMedical College of Wisconsin ALAmy LiThe University of Sydney JMJi Young MunKorea Brain Research Institute

Discussion

Member takes

Implication

Isoform-specific MyBP-C effects on Ca²⁺-dependent contractility extend mechanistic insights; human translation and therapeutic relevance remain open.

Structured PICO

Population

Preclinical models: permeabilized rat papillary muscle fibers (n=7-9 animals), mouse ventricular myosin and native thin filaments, reconstituted thin filaments, and adult rat ventricular myocytes (ARVM).

Intervention

Recombinant N-terminal fragments of MyBP-C isoforms (ssC1C2, fsC1C2, C0C2 at 0.10-10 µM) and adenoviral-mediated overexpression of full-length MyBP-C isoforms.

Comparator

Vehicle control, low Ca2+ control filaments, or uninfected controls.

Outcome

Thin filament activation, sliding velocities, force development, Ca2+ sensitivity, and relaxation kinetics.surrogate

Cardiac MyBP-C regulates contraction over a full range of Ca2+ levels, whereas slow- and fast-skeletal isoforms regulate contraction at lower and higher Ca2+ ranges, respectively.

Limitations

Use of N-terminal fragments in isolation may exaggerate functional effects outside the C-zone.
Predominant myosin isoforms in human hearts differ from those of the mouse models used.
Focus on thin filament interactions does not preclude effects of MyBP-C on myosin.
The focus on MyBP-C and the thin filament does not preclude the effect of MyBP-C on myosin

Cite This Study

Lin et al. (2018) studied Muscle contraction. Recombinant N-terminal fragments of MyBP-C isoforms (ssC1C2, fsC1C2, C0C2) vs. Untreated control was evaluated on Thin filament sliding velocity and force production at varying Ca2+ levels. Cardiac and slow-skeletal MyBP-C isoforms activate thin filament sliding at low Ca2+, whereas fast-skeletal and cardiac MyBP-C reduce sliding velocities and increase force production at higher Ca2+.

synapsesocial.com/papers/6a0909b814243797f79d0eb2 https://doi.org/10.1038/s41598-018-21053-1

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Implication

Isoform-specific MyBP-C effects on Ca²⁺-dependent contractility extend mechanistic insights; human translation and therapeutic relevance remain open.

Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca2+-dependent manner

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca2+-dependent manner

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider