Bertram Richard, Sherman Arthur
Department of Mathematics and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, USA.
Biophys J. 2004 Dec;87(6):3775-85. doi: 10.1529/biophysj.104.050955. Epub 2004 Oct 1.
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.
胰腺β细胞中的钙处理对于细胞内信号传导、电活动控制和胰岛素分泌至关重要。内质网（ER）是参与细胞内Ca2+储存和释放的关键细胞器。通过数学建模，我们分析了内质网的过滤特性，并阐明了它作为Ca2+源和Ca2+汇所起的双重作用。我们证明，最近关于胰岛和β细胞簇中游离Ca2+浓度的时间依赖性数据可以用一个模型来解释，该模型使用一个被动内质网，当细胞去极化且胞质Ca2+浓度升高时吸收Ca2+，当细胞复极化且胞质Ca2+浓度较低时释放Ca2+。我们发现，Ca2+诱导的Ca2+释放对于解释这些数据并非必要，实际上，如果Ca2+诱导的Ca2+释放是一个主导因素，该模型与数据不一致。最后，我们表明，一个包含内质网和质膜之间子空间隔室的三室模型与实验Ca2+数据的吻合度最佳。
