Mazel Tomás, Raymond Rebecca, Raymond-Stintz Mary, Jett Stephen, Wilson Bridget S
Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
Biophys J. 2009 Mar 4;96(5):1691-706. doi: 10.1016/j.bpj.2008.10.066.
Release of inflammatory mediators by mast cells in type 1 immediate-hypersensitivity allergic reactions relies on antigen-dependent increases in cytosolic calcium. Here, we used a series of electron microscopy images to build a 3D reconstruction representing a slice through a rat tumor mast cell, which then served as a basis for stochastic modeling of inositol-trisphosphate-mediated calcium responses. The stochastic approach was verified by reaction-diffusion modeling within the same geometry. Local proximity of the endoplasmic reticulum to either the plasma membrane or mitochondria is predicted to differentially impact local inositol trisphosphate receptor transport. The explicit consideration of organelle spatial relationships represents an important step toward building a comprehensive, realistic model of cellular calcium dynamics.
在1型速发型超敏反应中,肥大细胞释放炎症介质依赖于抗原诱导的胞质钙增加。在此,我们使用一系列电子显微镜图像构建了一个三维重建模型,该模型代表了大鼠肿瘤肥大细胞的一个切片,随后作为肌醇三磷酸介导的钙反应随机建模的基础。通过在相同几何结构内的反应扩散建模验证了随机方法。内质网与质膜或线粒体的局部接近程度预计会对局部肌醇三磷酸受体转运产生不同影响。对细胞器空间关系的明确考虑是构建细胞钙动力学综合、真实模型的重要一步。