Modeling of Ca2+ flux in pancreatic β-cells:: role of the plasma membrane and intracellular stores
Modeling of Ca2+ flux in pancreatic β-cells:: role of the plasma membrane and intracellular stores
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DOI：
10.1152/ajpendo.00194.2002
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发表时间：
2003-07-01
影响因子：
5.1
通讯作者：
Philipson, LH
中科院分区：
文献类型：
--
作者：
Fridlyand, LE;Tamarina, N;Philipson, LH
我们已经开发了β细胞中离子通量的详细数学模型，其中包括质膜中最重要的通道和泵。该模型耦合到描述Ca 2+，肌醇1，4，5-三磷酸（IP 3），ATP和Na+稳态的方程，包括内质网（ER）对Ca 2+的摄取和释放。在我们的模型中，代谢衍生的ATP通过调节ATP敏感的K+通道和质膜的去极化来激活向内的Ca 2+通量。模拟结果支持以下假设：ER中的细胞内Na+和Ca 2+可能是驱动快速（2-7 osc/min）和缓慢细胞内Ca 2+浓度振荡（0.3-0.9 osc/min）的主要变量，并且IP 3对ER中Ca 2+泄漏的影响有助于缓慢钙振荡的模式。模拟还表明，填充ER Ca 2+储存会导致更快的电爆发和Ca 2+振荡。还可以模拟分离的β细胞系中的特异性Ca 2+振荡。
We have developed a detailed mathematical model of ionic flux in beta-cells that includes the most essential channels and pumps in the plasma membrane. This model is coupled to equations describing Ca2+, inositol 1,4,5-trisphosphate (IP3), ATP, and Na+ homeostasis, including the uptake and release of Ca2+ by the endoplasmic reticulum (ER). In our model, metabolically derived ATP activates inward Ca2+ flux by regulation of ATP-sensitive K+ channels and depolarization of the plasma membrane. Results from the simulations support the hypothesis that intracellular Na+ and Ca2+ in the ER can be the main variables driving both fast (2-7 osc/min) and slow intracellular Ca2+ concentration oscillations (0.3-0.9 osc/min) and that the effect of IP3 on Ca2+ leak from the ER contributes to the pattern of slow calcium oscillations. Simulations also show that filling the ER Ca2+ stores leads to faster electrical bursting and Ca2+ oscillations. Specific Ca2+ oscillations in isolated beta-cell lines can also be simulated.