Filtering of Calcium Transients by the Endoplasmic Reticulum in Pancreatic Beta-cells
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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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Fletcher P, Thompson B, Liu C, Bertram R, Satin L, Sherman A Am J Physiol Endocrinol Metab. 2023; 324(6):E477-E487.
PMID: 37074988 PMC: 10228667. DOI: 10.1152/ajpendo.00030.2023.
Muller M, Walkling J, Seemann N, Rustenbeck I Int J Mol Sci. 2023; 24(4).
PMID: 36834618 PMC: 9960854. DOI: 10.3390/ijms24043206.
Li M, Shao F, Qian Q, Yu W, Zhang Z, Chen B Mol Ther Nucleic Acids. 2021; 26:307-320.
PMID: 34513312 PMC: 8416971. DOI: 10.1016/j.omtn.2021.06.027.
Experimental induction and mathematical modeling of dynamics in rat round spermatids.
Saavedra J, Reyes J, Salinas D Channels (Austin). 2020; 14(1):347-361.
PMID: 33026280 PMC: 7757827. DOI: 10.1080/19336950.2020.1826787.
Muller M, Glombek M, Powitz J, Bruning D, Rustenbeck I Cells. 2020; 9(6).
PMID: 32570905 PMC: 7348896. DOI: 10.3390/cells9061487.