Full muscle relaxation happens when [Ca²⁺] falls below the threshold for force activation. Several experimental models, from whole muscle organs and intact muscle down to skinned fibers, have been used to explore the cascade of kinetic events leading to mechanical relaxation. The use of single myofibrils together with fast solution switching techniques, has provided new information about the role of cross-bridge (CB) dissociation in the time course of isometric force decay. Myofibril’s relaxation is biphasic starting with a slow seemingly linear phase, with a rate constant, slow k_REL, followed by a fast mono-exponential phase. Sarcomeres remain isometric during the slow force decay that reflects CB detachment under isometric conditions while the final fast relaxation phase begins with a sudden give of few sarcomeres and is then dominated by intersarcomere dynamics. Based on a simple two-state model of the CB cycle, myofibril slow k_REL represents the apparent forward rate with which CBs leave force generating states (g_app) under isometric conditions and correlates with the energy cost of tension generation (ATPase/tension ratio); in short slow k_REL ~ g_app ~ tension cost. The validation of this relationship is obtained by simultaneously measuring maximal isometric force and ATP consumption in skinned myocardial strips that provide an unambiguous determination of the relation between contractile and energetic properties of the sarcomere. Thus, combining kinetic experiments in isolated myofibrils and mechanical and energetic measurements in multicellular cardiac strips, we are able to provide direct evidence for a positive linear correlation between myofibril isometric relaxation kinetics (slow k_REL) and the energy cost of force production both measured in preparations from the same cardiac sample. This correlation remains true among different types of muscles with different ATPase activities and also when CB kinetics are altered by cardiomyopathy-related mutations. Sarcomeric mutations associated to hypertrophic cardiomyopathy (HCM), a primary cardiac disorder caused by mutations in genes encoding sarcomeric proteins, have been often found to accelerate CB turnover rate and increase the energy cost of myocardial contraction. Here we review data showing that faster CB detachment results in a proportional increase in the energetic cost of tension generation in heart samples from both HCM patients and mouse models of the disease.

当 [Ca ²⁺ ] 低于力激活阈值时，会发生完全肌肉松弛。几个实验模型，从整个肌肉器官和完整肌肉到皮肤纤维，已被用于探索导致机械松弛的动力学事件的级联。单肌原纤维与快速溶液切换技术一起使用，提供了有关横桥 (CB) 解离在等长力衰减时间过程中的作用的新信息。肌原纤维的松弛是双相的，从一个缓慢的看似线性的阶段开始，具有一个速率常数，慢k _REL，然后是快速的单指数阶段。在等长条件下反映 CB 脱离的缓慢力衰减期间，肌节保持等长，而最终的快速松弛阶段开始时突然出现少量肌节，然后由肌节间动力学控制。基于 CB 循环的简单双态模型，肌原纤维慢k _REL表示在等距条件下CB 离开力生成状态 ( g _app )的表观正向速率，并与产生张力的能量成本（ATPase/张力比）相关); 总之慢k _REL  ~  g _app ～张力成本。这种关系的验证是通过同时测量最大等长力和 ATP 消耗在皮肤心肌条中获得的，这些条带明确确定了肌节的收缩特性和能量特性之间的关系。因此，结合分离肌原纤维的动力学实验和多细胞心脏条带的机械和能量测量，我们能够为肌原纤维等长舒张动力学（慢k _REL）之间的正线性相关性提供直接证据) 和力量产生的能量成本都在同一心脏样本的制备中测量。这种相关性在具有不同 ATP 酶活性的不同类型肌肉之间以及当心肌病相关突变改变 CB 动力学时仍然存在。与肥厚性心肌病 (HCM) 相关的肌节突变是一种由编码肌节蛋白的基因突变引起的原发性心脏病，经常被发现会加速 CB 周转率并增加心肌收缩的能量成本。在这里，我们审查的数据显示，更快的 CB 脱离导致来自 HCM 患者和该疾病小鼠模型的心脏样本中张力产生的能量成本成比例增加。