Filtering of calcium transients by the endoplasmic reticulum in pancreatic beta-cells.
Calcium handling in pancreatic beta-cells is important for intracellular signaling, the control of electrical activity, and insulin secretion. The endoplasmic reticulum (ER) is a key organelle involved in the storage and release of intracellular Ca2+. Using mathematical modeling, we analyze the filtering properties of the ER and clarify the dual role that it plays as both a Ca2+ source and a Ca2+ sink. We demonstrate that recent time-dependent data on the free Ca2+ concentration in pancreatic islets and beta-cell clusters can be explained with a model that uses a passive ER that takes up Ca2+ when the cell is depolarized and the cytosolic Ca2+ concentration is elevated, and releases Ca2+ when the cell is repolarized and the cytosolic Ca2+ is at a lower concentration. We find that Ca2+-induced Ca2+ release is not necessary to explain the data, and indeed the model is inconsistent with the data if Ca2+-induced Ca2+ release is a dominating factor. Finally, we show that a three-compartment model that includes a subspace compartment between the ER and the plasma membrane provides the best agreement with the experimental Ca2+ data.
Department of Mathematics and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, USA. bertram@math.fsu.edu
Richard
R
Bertram
Arthur
A
Sherman
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D008657:Metabolic Clearance Rate; D008954:Models, Biological
D015220:Calcium Channels; D002118:Calcium