Irving Malcolm
Randall Centre for Cell and Molecular Biophysics and BHF Centre for Research Excellence, King's College London, London, UK.
Nat Rev Cardiol. 2025 Jan;22(1):9-19. doi: 10.1038/s41569-024-01063-5. Epub 2024 Jul 19.
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.
心脏的收缩由肌球蛋白和肌动蛋白丝之间由ATP水解驱动的周期性相互作用所推动。心肌的模块化结构和心跳在器官水平上的同步性确保了这种肌球蛋白ATP酶循环与宏观心动周期之间紧密的相互耦合。肌球蛋白马达响应肌动蛋白和肌球蛋白丝的周期性激活，以驱动控制心脏腔室流入和流出瓣膜的压力变化。瓣膜的开闭又使肌球蛋白马达在大致等长收缩模式和大致等张收缩模式之间切换。尽管两种肌肉类型中的肌球蛋白丝具有相同数量的肌球蛋白马达，但心脏中的细丝应力峰值远小于完全激活的骨骼肌中的应力峰值。计算表明，心脏中仅约5%的肌球蛋白马达就需要产生收缩压峰值，尽管驱动射血需要更多的马达。对活跃马达数量的严格调节对于健康心脏的有效运作至关重要——这种控制通常会因与遗传性心脏病相关的基因变异而受到破坏，恢复这种控制可能是新型疗法开发的一个有用终点。
