Stochastic modeling of calcium in 3D geometry.
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.
Mazel
Tomás
T
Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
Raymond
Rebecca
R
Raymond-Stintz
Mary
M
Jett
Stephen
S
Wilson
Bridget S
BS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology; D003198:Computer Simulation; D004058:Diffusion; D004721:Endoplasmic Reticulum / Q000502:physiology; D021621:Imaging, Three-Dimensional; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological; D051381:Rats; D013269:Stochastic Processes
D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; C516441:inositol trispyrophosphate; D002118:Calcium