title: Reaction diffusion modeling of calcium dynamics with realistic ER geometry.
abstract: 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.
authors.affiliation: Sandia National Laboratory, Albuquerque, New Mexico, USA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Means
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Jason
authors.initials: J
authors.lastname: Shepherd
authors.forename: John
authors.initials: J
authors.lastname: Shadid
authors.forename: John
authors.initials: J
authors.lastname: Fowler
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Wojcikiewicz
authors.forename: Tomas
authors.initials: T
authors.lastname: Mazel
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Smith
authors.forename: Bridget S
authors.initials: BS
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D037282:Calreticulin / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003593:Cytoplasm / Q000502:physiology / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000502:physiology* / Q000648:ultrastructure; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating / Q000502:physiology; D008407:Mast Cells / Q000502:physiology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D015220:Calcium Channels; D002147:Calmodulin; D037282:Calreticulin; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium