A simple numerical model of calcium spark formation and detection in cardiac myocytes
A simple numerical model of calcium spark formation and detection in cardiac myocytes
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DOI：
10.1016/s0006-3495(98)77491-0
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发表时间：
1998-07-01
影响因子：
3.4
通讯作者：
Cheng, HP
中科院分区：
文献类型：
--
作者：
Smith, GD;Keizer, JE;Cheng, HP
心肌兴奋收缩偶联的基本事件是由肌浆网(SR)中的一个或多个兰尼定受体产生的钙火花。在这里，我们构建了一个简单的数值模型来探索心肌细胞中钙离子火花的形成、检测和解释。该模型包括Ca~(2+)释放、胞浆扩散、SR Ca~(2+)-ATPase的重定位，以及Ca~(2+)与内源性Ca~(2+)结合部位和可扩散指示剂(Fluo-3)的结合和解离。在均匀、各向同性的胞浆中的模拟再现了典型的心脏钙离子火花的亮度和时间过程，但低估了其空间大小(类似于1.1微米对类似于2.0微米)。即使在使用无模糊荧光数据时，通过假设与指示剂的平衡来反向计算[Ca~(2+)](I)也不能很好地估计游离Ca~(2+)浓度。参数敏感性研究表明，指示剂的迁移率、动力学和浓度是决定钙火花形状的重要因素，而固定的缓冲液和泵的影响较小。使用几何上更复杂的模型，我们表明，钙离子的不对称形状可以用钙离子和指示剂染料的各向异性扩散更好地解释，而不是用钙缓冲和运输系统的肌下不均匀来解释。此外，我们还考察了离心共焦采样对火花统计量方差的贡献。
The elementary events of excitation-contraction coupling in heart muscle are Ca2+ sparks, which arise from one or more ryanodine receptors in the sarcoplasmic reticulum (SR). Here a simple numerical model is constructed to explore Ca2+ spark formation, detection, and interpretation in cardiac myocytes. This model includes Ca2+ release, cytosolic diffusion, resequestration by SR Ca2+-ATPases, and the association and dissociation of Ca2+ with endogenous Ca2+-binding sites and a diffusible indicator dye (fluo-3). Simulations in a homogeneous, isotropic cytosol reproduce the brightness and the time course of a typical cardiac Ca2+ spark, but underestimate its spatial size (similar to 1.1 mu m VS similar to 2.0 mu m). Back-calculating [Ca2+](i) by assuming equilibrium with indicator fails to provide a good estimate of the free Ca2+ concentration even when using blur-free fluorescence data. A parameter sensitivity study reveals that the mobility, kinetics, and concentration of the indicator are essential determinants of the shape of Ca2+ sparks, whereas the stationary buffers and pumps are less influential, Using a geometrically more complex version of the model, we show that the asymmetric shape of Ca2+ sparks is better explained by anisotropic diffusion of Ca2+ ions and indicator dye rather than by subsarcomeric inhomogeneities of the Ca2+ buffer and transport system. In addition, we examine the contribution of off-center confocal sampling to the variance of spark statistics.