Nordin C
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
Am J Physiol. 1993 Dec;265(6 Pt 2):H2117-36. doi: 10.1152/ajpheart.1993.265.6.H2117.
This paper presents the equations and responses of a mathematical model that simulates the transmembrane current and intracellular concentrations of Ca2+ ([Ca2+]), Na+ ([Na+]), and K+ ([K+]) of an isolated guinea pig myocyte. The structure of the model is closely related to the formulation of DiFrancesco and Noble (9). Quantitative values are based on a large number of experimental constraints, taken from the literature on isolated myocytes as well as our own experimental studies, that describe the properties of individual channels and integrated responses of whole cells under a variety of conditions. The model was constructed as a homeostatic system. The equilibrium of the model corresponds to the resting potential and intracellular ionic concentrations of unstimulated myocytes. The model generates deviations from equilibrium corresponding to the behavior of cells after stimulation of action potentials at different rates, blockade of Na-K-adenosinetriphosphatase (ATPase), reduction in extracellular [K+], and injection of constant depolarizing current. Simulations from the model suggest that changes in myoplasmic [Ca2+] at different stimulation rates, the generation of restitution and postextrasystolic potentiation, and the development of intracellular [Ca2+] oscillations arise simply from different interactions between uptake of Ca2+ into the sarcoplasmic reticulum via the Ca(2+)-ATPase, Ca(2+)-induced Ca2+ release of Ca2+ into the myoplasm, flux between regions of uptake and release, and leakage between sarcoplasmic reticulum and myoplasm. The model also demonstrates that a wide variety of basic electrophysiological responses of the isolated guinea pig myocyte can be simulated with quantitative precision by a single set of equations based on experimentally measured transmembrane current and intracellular [Ca2+] and [Na+].
本文介绍了一个数学模型的方程和响应，该模型模拟了分离的豚鼠心肌细胞的跨膜电流以及细胞内钙离子（[Ca2+]）、钠离子（[Na+]）和钾离子（[K+]）的浓度。该模型的结构与迪弗朗西斯科和诺布尔（9）的公式密切相关。定量值基于大量实验约束条件，这些条件取自关于分离心肌细胞的文献以及我们自己的实验研究，描述了单个通道的特性以及在各种条件下整个细胞的综合响应。该模型被构建为一个稳态系统。模型的平衡对应于未受刺激心肌细胞的静息电位和细胞内离子浓度。该模型产生与平衡的偏差，这与以不同速率刺激动作电位、阻断钠钾三磷酸腺苷酶（ATP酶）、降低细胞外[K+]以及注入恒定去极化电流后细胞的行为相对应。该模型的模拟结果表明，在不同刺激速率下肌浆[Ca2+]的变化、恢复和早搏后增强的产生以及细胞内[Ca2+]振荡的发展仅仅源于通过钙（2+）-ATP酶将Ca2+摄取到肌浆网、Ca2+诱导的Ca2+释放到肌浆、摄取和释放区域之间的通量以及肌浆网和肌浆之间的泄漏等不同相互作用。该模型还表明，基于实验测量的跨膜电流以及细胞内[Ca2+]和[Na+]，通过一组单一的方程可以精确地模拟分离的豚鼠心肌细胞的各种基本电生理响应。
