Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio, USA.
Biophys J. 2013 Apr 16;104(8):1752-63. doi: 10.1016/j.bpj.2013.02.025.
A mathematical model that integrates the dynamics of cell membrane potential, ion homeostasis, cell volume, mitochondrial ATP production, mitochondrial and endoplasmic reticulum Ca(2+) handling, IP3 production, and GTP-binding protein-coupled receptor signaling was developed. Simulations with this model support recent experimental data showing a protective effect of stimulating an astrocytic GTP-binding protein-coupled receptor (P2Y1Rs) following cerebral ischemic stroke. The model was analyzed to better understand the mathematical behavior of the equations and to provide insights into the underlying biological data. This approach yielded explicit formulas determining how changes in IP3-mediated Ca(2+) release, under varying conditions of oxygen and the energy substrate pyruvate, affected mitochondrial ATP production, and was utilized to predict rate-limiting variables in P2Y1R-enhanced astrocyte protection after cerebral ischemic stroke.
建立了一个数学模型，该模型整合了细胞膜电位、离子动态平衡、细胞容积、线粒体 ATP 生成、线粒体和内质网 Ca(2+)处理、IP3 生成以及 G 蛋白偶联受体信号的动力学。该模型的模拟结果支持了最近的实验数据，表明在脑缺血性中风后刺激星形胶质细胞 G 蛋白偶联受体 (P2Y1Rs)具有保护作用。对该模型进行了分析，以更好地理解方程的数学行为，并深入了解潜在的生物学数据。这种方法产生了明确的公式，可确定在不同氧和能量底物丙酮酸条件下 IP3 介导的 Ca(2+)释放的变化如何影响线粒体 ATP 的生成，并利用该方法预测脑缺血性中风后 P2Y1R 增强星形胶质细胞保护的限速变量。
