Modeling of protein interactions involved in cardiac tension development
Modeling of protein interactions involved in cardiac tension development
复制标题
DOI：
10.1142/s0218127403008855
复制
发表时间：
2003-12-01
影响因子：
2.2
通讯作者：
Seemann, G
中科院分区：
文献类型：
--
作者：
Sachse, FB;Glänzel, KG;Seemann, G
对负责心脏张力发展的蛋白质相互作用进行建模可以增强对心脏生理和病理生理现象的理解。肌张力发展的主要成分是肌动蛋白、肌球蛋白、肌钙蛋白和原肌球蛋白。张力是通过使用三磷酸腺苷作为能量来源的肌动蛋白和肌球蛋白的跨桥循环产生的。跨桥循环是通过细胞内钙与肌钙蛋白的结合启动的，导致原肌球蛋白的构型变化。在这项工作中，基于最近对蛋白质水平的测量和描述，推导了心脏张力发展中蛋白质相互作用的混合模型。纳入了对细胞内钙浓度、肌节拉伸和拉伸速度以及协同机制的依赖性。该模型通过与所涉及蛋白质的配置相关的状态来量化张力的发展。该模型能够与心肌细胞的电生理学模型相结合，重建机电现象。使用混合模型进行了数值模拟，说明了稳态和长度开关实验的重建。稳态实验描述了完整大鼠心脏小梁中的力-胞质 [Ca2+] 关系。长度转换实验提供了兔右心室乳头肌突然拉伸后力量重建的数据。数值模拟的结果与实验研究定量一致。心脏张力发展的混合模型为进一步的心脏机电模型提供了接口。该混合模型可以与细胞电生理学和心肌被动力学模型相结合，从而包含机电反馈机制。该混合模型可用于阐明张力发展的协同机制、病理生理变化和代谢。
Modeling of protein interactions responsible for cardiac tension development can enhance the understanding of physiological and pathophysiological phenomena of the heart. Principal components of muscular tension development are the proteins actin, myosin, troponin and tropomyosin. The tension is produced by cross-bridge cycling of actin and myosin using adenosine triphosphate as energy source. The cross-bridge cycling is initiated by binding of intracellular calcium to troponin, resulting in configuration changes of tropomyosin.In this work a hybrid model of protein interactions in cardiac tension development is derived on basis of recent measurements and descriptions on protein level. Dependencies on intracellular calcium concentration, sarcomere stretch and stretch velocity as well as cooperativity mechanisms are incorporated. The model quantifies the tension development by states associated to configurations of the involved proteins. The model enables in conjunction with electrophysiological models of cardiac myocytes the reconstruction of electro-mechanical phenomena. Numerical simulations with the hybrid model were performed, which illustrated the reconstruction of steady state and length switches experiments. The steady state experiments describe the force-cytosolic [Ca2+] relationship in intact rat cardiac trabeculae. The length switch experiments provide data on the redevelopment of force after sudden stretch in rabbit right ventricular papillary muscles. Results of the numerical simulations show quantitative agreement with experimental studies.The hybrid model of cardiac tension development offers interfaces to further models of cardiac electro-mechanics. The hybrid model can be coupled with models of cellular electrophysiology and passive mechanics of myocardium allowing the inclusion of mechano-electrical feedback mechanisms. The hybrid model can be applied to elucidate cooperativity mechanisms, pathophysiological changes and metabolism of tension development.