Filtering of calcium Transients by the Endoplasmic Reticulum in Pancreatic Beta-Cells

Richard Bertram and Arthur Sherman

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 calcium. Using mathematical modeling, we analyze the filtering properties of the ER and clarify the dual role that it plays as both a calcium source and a calcium sink. We demonstrate that recent time-dependent data on the free calcium concentration in pancreatic islets and beta-cell clusters can be explained with a model that uses a passive ER that takes up calcium when the cell is depolarized and the cytosolic calcium concentration is elevated, and releases calcium when the cell is repolarized and the cytosolic calcium is at a lower concentration. We find that calcium-induced calcium release is not necessary to explain the data, and indeed the model is inconsistent with the data if calcium-induced calcium 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 calcium data.