8638649

pubmed:Citation

3 Pt 1

We undertake a quantitative investigation of changes in intracellular free Ca2+ concentration ([Ca2+]i) in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells, which include contributions of both Ca2+ store release and Ca2+ influx from the medium. Following Keizer and De Young (J. Keizer and G. De Young. Biophys. J. 61: 649-660, 1992), we develop a highly constrained mathematical model for [Ca2+]i oscillations in RBL-2H3 cells, which includes activation of the inositol trisphosphate receptor (IP3R) by inositol 1,4,5-trisphospate, indirect Ca2+ activation of the IP3R via Ca2+ -dependent activity of phospholipase C-gamma, slow inhibition of the IP3R by cytosolic Ca2+, refilling of Ca2+ stores by a Ca2+ -ATPase (SERCA)-type pump, and a simple representation of the dependence of plasma membrane (PM) fluxes on experimental conditions. Using this full (open cell) model, we simulate [Ca2+]i responses for protocols in which antigen concentration and external Ca2+ are manipulated and compare out calculations with experimental data. In protocol A, cells are stimulated in the presence of external Ca2+, in protocols B and C, cells are stimulated in the absence of external Ca2+, with external Ca2+ later reapplied in protocol C. We are able to reproduce quantitatively the important features of all three protocols, including the dose response of protocol B, the [Ca2+]i response to thapsigargin, and lag time results, and we provide qualitative explanations for the responses derived from our calculations. We also develop a simplified (closed cell) version of the model in which PM fluxes are neglected and total free Ca2+ concentration ([Ca2+]T) is a slowly varying parameter. This permits us to explain in a simple graphical fashion how PM fluxes may influence [Ca2+]i responses in RBH-2H3 cells through modulation of [Ca2+]T.

eng

IM

MEDLINE

0002-9513

Print

NLM

C939-52

pubmed-meshheading:8638649-Animals, pubmed-meshheading:8638649-Antigens, pubmed-meshheading:8638649-Biological Transport, pubmed-meshheading:8638649-Calcium, pubmed-meshheading:8638649-Calcium Channels, pubmed-meshheading:8638649-Calcium-Transporting ATPases, pubmed-meshheading:8638649-Cell Line, pubmed-meshheading:8638649-Cell Membrane, pubmed-meshheading:8638649-Cytosol, pubmed-meshheading:8638649-Dinitrophenols, pubmed-meshheading:8638649-Inositol 1,4,5-Trisphosphate, pubmed-meshheading:8638649-Inositol 1,4,5-Trisphosphate Receptors, pubmed-meshheading:8638649-Kinetics, pubmed-meshheading:8638649-Leukemia, Basophilic, Acute, pubmed-meshheading:8638649-Mathematics, pubmed-meshheading:8638649-Models, Biological, pubmed-meshheading:8638649-Rats, pubmed-meshheading:8638649-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:8638649-Serum Albumin, Bovine, pubmed-meshheading:8638649-Tumor Cells, Cultured, pubmed-meshheading:8638649-Type C Phospholipases

Effect of Ca2+ influx on intracellular free Ca2+ responses in antigen-stimulated RBL-2H3 cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't