Landesberg A, Sideman S
Heart System Research Center, Julius Silver Institute, Haifa, Israel.
Am J Physiol. 1994 Aug;267(2 Pt 2):H779-95. doi: 10.1152/ajpheart.1994.267.2.H779.
This study describes the regulation of mechanical activity in the intact cardiac muscle, the effects of the free calcium transients and the mechanical constraints, and emphasizes the central role of the troponin complex in regulating muscle activity. A "loose coupling" between calcium binding to troponin and cross-bridge cycling is stipulated, allowing the existence of cross bridges in the strong conformation without having bound calcium on the neighboring troponin. The model includes two feedback mechanisms: 1) a positive feedback, or cooperativity, in which the cycling cross bridges affect the affinity of troponin for calcium, and 2) a negative mechanical feedback, where the filament-sliding velocity affects cross-bridge cycling. The model simulates the reported experimental force-length and force-velocity relationships at different levels of activation. The dependence of the shortening velocity on calcium concentration, sarcomere length, internal load, and rate of cross-bridge cycling is described analytically in agreement with reported data. Furthermore, the model provides an analytic solution for Hill's equation of the force-velocity relationship and for the phenomena of unloaded shortening velocity and force deficit. The model-calculated changes in free calcium in various mechanical conditions are in good agreement with the available experimental results.
本研究描述了完整心肌中机械活动的调节、游离钙瞬变和机械约束的影响，并强调了肌钙蛋白复合体在调节肌肉活动中的核心作用。文中提出钙与肌钙蛋白结合和横桥循环之间存在“松散耦合”，这使得在相邻肌钙蛋白上没有结合钙的情况下，仍能存在处于强构象的横桥。该模型包括两种反馈机制：1）正反馈或协同作用，即循环的横桥影响肌钙蛋白对钙的亲和力；2）负机械反馈，即细丝滑动速度影响横桥循环。该模型模拟了在不同激活水平下所报道的实验力-长度和力-速度关系。分析描述了缩短速度对钙浓度、肌节长度、内部负荷和横桥循环速率的依赖性，与报道数据一致。此外，该模型为希尔力-速度关系方程以及无负荷缩短速度和力亏现象提供了解析解。模型计算得出的各种机械条件下游离钙的变化与现有实验结果高度吻合。
