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Functional control of myosin motors in the cardiac cycle

Nature Reviews Cardiology (2024)Cite this article

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Abstract

Contraction of the heart is driven by cyclical interactions between myosin and actin filaments powered by ATP hydrolysis. The modular structure of heart muscle and the organ-level synchrony of the heartbeat ensure tight reciprocal coupling between this myosin ATPase cycle and the macroscopic cardiac cycle. The myosin motors respond to the cyclical activation of the actin and myosin filaments to drive the pressure changes that control the inflow and outflow valves of the heart chambers. Opening and closing of the valves in turn switches the myosin motors between roughly isometric and roughly isotonic contraction modes. Peak filament stress in the heart is much smaller than in fully activated skeletal muscle, although the myosin filaments in the two muscle types have the same number of myosin motors. Calculations indicate that only ~5% of the myosin motors in the heart are needed to generate peak systolic pressure, although many more motors are needed to drive ejection. Tight regulation of the number of active motors is essential for the efficient functioning of the healthy heart — this control is commonly disrupted by gene variants associated with inherited heart disease, and its restoration might be a useful end point in the development of novel therapies.

Key points

  • The modular structure of heart muscle and the organ-level synchrony of the heartbeat ensure tight reciprocal coupling between the myosin ATPase cycle and the macroscopic cardiac cycle.

  • Only ~5% of the myosin motors in the heart are needed to generate peak systolic pressure.

  • The balance between the number of active motors and the molecular parameters of the myosin ATPase cycle enables the healthy heart to work at maximum efficiency.

  • Genetic variants associated with inherited heart disease disrupt that balance, and restoring the balance might be a useful end point in the development of novel therapies.

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Fig. 1: The sarcomere and the main protein constituents of the thin and thick filaments.
Fig. 2: The cardiac cycle at the organ level.
Fig. 3: The cardiac cycle at the filament level.
Fig. 4: The myosin motor cycle.

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Acknowledgements

The author thanks the Wellcome Trust and UK Medical Research Council for financial support, and E. Brunello, P. Chowienczyk, L. Fusi and M. Gautel (all from King’s College London, UK), J. Ellis (University College London, UK) and T. Kampourakis (University of Kentucky, USA) for comments on an earlier version of the manuscript.

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    Malcolm Irving

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Irving, M. Functional control of myosin motors in the cardiac cycle. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-024-01063-5

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