Reaction diffusion modeling of calcium dynamics with realistic ER geometry
Reaction diffusion modeling of calcium dynamics with realistic ER geometry
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DOI：
10.1529/biophysj.105.075036
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发表时间：
2006-07-15
影响因子：
3.4
通讯作者：
Wilson, Bridget S.
中科院分区：
文献类型：
--
作者：
Means, Shawn;Smith, Alexander J.;Wilson, Bridget S.
我们描述了肥大细胞钙动力学的有限元模型，该模型结合了内质网的复杂几何形状。该模型建立在电子断层扫描倾斜序列的内质网(ER)的三维重建基础上。四面体网格提供了ER管腔、ER膜、细胞质和质膜的体积表示。反应-扩散模型同时跟踪细胞质和内质网内钙浓度的变化，并包括管腔和细胞质蛋白缓冲液。通过PMCA、SERCA、内质网渗漏和II型IP3受体的转运也被显示。该模型的独特功能包括IP3受体钙通道的随机行为，以及当内质网表面弥漫分布或聚集成簇时通道开放时间的比较。模拟结果表明，近距离的IP3R通道通过局部的钙离子反馈效应来调节相邻通道的活动。在IP3介导的弥散构型受体释放后，胞浆钙水平升高，内质网钙浓度下降。模拟结果还表明，内质网的缓冲能力，而不是限制扩散，是影响平均管腔钙浓度的主要因素。
We describe a finite-element model of mast cell calcium dynamics that incorporates the endoplasmic reticulum's complex geometry. The model is built upon a three-dimensional reconstruction of the endoplasmic reticulum ( ER) from an electron tomographic tilt series. Tetrahedral meshes provide volumetric representations of the ER lumen, ER membrane, cytoplasm, and plasma membrane. The reaction-diffusion model simultaneously tracks changes in cytoplasmic and ER intraluminal calcium concentrations and includes luminal and cytoplasmic protein buffers. Transport fluxes via PMCA, SERCA, ER leakage, and Type II IP3 receptors are also represented. Unique features of the model include stochastic behavior of IP3 receptor calcium channels and comparisons of channel open times when diffusely distributed or aggregated in clusters on the ER surface. Simulations show that IP3R channels in close proximity modulate activity of their neighbors through local Ca2+ feedback effects. Cytoplasmic calcium levels rise higher, and ER luminal calcium concentrations drop lower, after IP3-mediated release from receptors in the diffuse configuration. Simulation results also suggest that the buffering capacity of the ER, and not restricted diffusion, is the predominant factor influencing average luminal calcium concentrations.