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.