Namba T, Takaki M, Araki J, Ishioka K, Akashi T, Zhao L Y, Matsushita T, Ito H, Fujii W, Matsubara H
Second Department of Physiology, Okayama University Medical School, Japan.
Jpn Heart J. 1993 Sep;34(5):601-16. doi: 10.1536/ihj.34.601.
Myocardial Ca2+ handling during excitation-contraction coupling has been modelled mathematically to gain a better insight into the expectation that Ca2+ sensitization of contractile machinery may save myocardial energy utilization for Ca2+ handling. The basic model of myocardial Ca2+ kinetics and mechanoenergetics involved the sarcoplasmic reticulum (SR), sarcoplasm, troponin C (Tn) and crossbridges (CB). The relations among the released Ca2+ ions from the SR, peak concentrations of sarcoplasmic free Ca2+ ([Ca2+]i) and Ca(2+)-bound troponin ([TnCa]) and peak contractile force were computed, based upon the assumptions that the released Ca2+ ions diffuse as free Ca2+ in sarcoplasm, bind kinetically with Tn with an association rate constant of k1, dissociate from TnCa with a dissociation rate constant of k2, and are sequestered into the SR with consumption of ATP. TnCa was associated with CB cycling to develop force with a set of given on and off rate constants. The association constant Ka (= k1/k2) of TnCa as an index of Ca2+ sensitivity of Tn was varied 32-fold from 0.25 to 8/microM. Results showed that Ca2+ sensitization from a lower Ka level could most sharply decrease the total Ca2+ release required to develop the same contractile force. Thus, it would reduce the total Ca2+ handling energy that the SR uses to maintain the same contractility.
在兴奋-收缩偶联过程中，对心肌钙离子处理进行了数学建模，以便更好地理解收缩机制的钙离子敏化可能节省心肌用于钙离子处理的能量消耗这一预期。心肌钙离子动力学和机械能量学的基本模型涉及肌浆网（SR）、肌浆、肌钙蛋白C（Tn）和横桥（CB）。基于以下假设计算从SR释放的钙离子、肌浆游离钙离子（[Ca2+]i）和钙离子结合肌钙蛋白（[TnCa]）的峰值浓度与峰值收缩力之间的关系：释放的钙离子在肌浆中以游离钙离子形式扩散，以结合速率常数k1与Tn进行动力学结合，以解离速率常数k2从TnCa解离，并在消耗ATP的情况下被隔离到SR中。TnCa与CB循环相关联，以一组给定的开启和关闭速率常数产生力。作为Tn钙离子敏感性指标的TnCa的结合常数Ka（=k1/k2）从0.25到8/μM变化了32倍。结果表明，从较低的Ka水平进行钙离子敏化能够最显著地降低产生相同收缩力所需的总钙离子释放量。因此，这将减少SR用于维持相同收缩性的总钙离子处理能量。
