Negroni Jorge A, Lascano Elena C
Department of Physiology, Pharmacology and Biochemistry, Favaloro University, Buenos Aires, Argentina.
J Mol Cell Cardiol. 2008 Aug;45(2):300-12. doi: 10.1016/j.yjmcc.2008.04.012. Epub 2008 May 3.
A cardiac muscle model is presented with the purpose of representing a wide range of mechanical experiments at constant and transient Ca(2+) concentration. Modifications of a previous model were: weak and power attached crossbridge states, a troponin system involving three consecutive regulatory troponin-tropomyosin units acting together in Ca(2+) kinetics and detachment constants depending on crossbridge length. This model improved cooperativity (Hill coefficient close to 4) and the force-velocity relationship, and incorporated the representation of the four phases of muscle response to length and force steps, isotonic shortening and isosarcometric contractions, preserving previous satisfactory results. Moreover, experimentally reported effects, such as length dependence on Ca(2+) affinity, the decreased cooperativity at higher Ca(2+) concentrations, temperature effects on the stiffness-frequency relationship and the isometric internal shortening due to series elasticity, were obtained. In conclusion, the model is more comprehensive than a previous version because it is able to represent a wider variety of steady state experiments, the mechanical variables in twitches can be adequately related to intracellular Ca(2+), and all the simulations were performed with the same set of parameters.
提出了一种心肌模型,目的是在恒定和瞬态Ca(2+)浓度下呈现广泛的力学实验。对先前模型的修改包括:弱结合和强结合横桥状态、一个肌钙蛋白系统,该系统涉及三个连续的调节性肌钙蛋白-原肌球蛋白单元,它们在Ca(2+)动力学中共同作用,以及取决于横桥长度的解离常数。该模型改善了协同性(希尔系数接近4)和力-速度关系,并纳入了肌肉对长度和力阶跃、等张收缩和等肌节收缩的四个反应阶段的表示,同时保留了先前令人满意的结果。此外,还获得了实验报道的效应,如长度对Ca(2+)亲和力的依赖性、较高Ca(2+)浓度下协同性的降低、温度对刚度-频率关系的影响以及由于串联弹性导致的等长内部缩短。总之,该模型比先前版本更全面,因为它能够表示更广泛的稳态实验,抽搐中的力学变量可以与细胞内Ca(2+)充分关联,并且所有模拟均使用同一组参数进行。