Filtering of Calcium Transients by the Endoplasmic Reticulum in Pancreatic β-Cells

Department of Mathematics and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, USA.
Biophysical Journal (Impact Factor: 3.83). 01/2005; 87(6):3775-85. DOI: 10.1529/biophysj.104.050955
Source: PubMed

ABSTRACT 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.

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    • "Details of the equations are provided in the appendix. The K(ATP) current has been added to the V equation, and the Ca equation now has terms for exchange with the endoplasmic reticulum, which impart a slow component to Ca that is transmitted to I K(Ca) [6] [7]. The ADP equation models the production of ATP from ADP in the mitochondria, which is inhibited with a slow time constant by Ca 2+ via shunting of the mitochondrial membrane potential [18]. "
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