MODELING RECEPTOR-CONTROLLED INTRACELLULAR CALCIUM OSCILLATORS
MODELING RECEPTOR-CONTROLLED INTRACELLULAR CALCIUM OSCILLATORS
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DOI：
10.1016/0143-4160(91)90012-4
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发表时间：
1991-02-01
期刊：
影响因子：
4
通讯作者：
CHAY, TR
中科院分区：
文献类型：
--
作者：
CUTHBERTSON, KSR;CHAY, TR
本文提出了数学模型的肝细胞钙振荡器，遵循的概念，在一类非正式的模型开发帐户的显着依赖于受体类型的几个功能的钙振荡，特别是形状和持续时间的游离钙瞬变。 这些模型的本质是，瞬变应该由激活的GTP结合蛋白的积累来计时，其与正反馈过程以及可能的协同效应相结合，导致磷脂酶C（PLC）的突然激活，随后是负反馈过程，其关闭钙升高并导致游离钙下降回到静息水平。 这些模型预测肌醇（1，4，5）P3以及游离钙的脉动振荡。 我们表明，受体控制的细胞内钙振荡器涉及一个未知的正反馈途径PLC和负反馈从蛋白激酶C（PKC）到G-蛋白和受体，或负反馈刺激GTdR活性可以刺激观察到的细胞内钙振荡的许多功能。 这些振荡器表现出频率对激动剂浓度的依赖性和瞬态持续时间对受体和G蛋白类型的依赖性。 我们还表明，PLC依赖的GT3激活因子（GAF）可以提供一些其他令人费解的功能的细胞内钙振荡的解释。
This paper presents mathematical models for the hepatocyte calcium oscillator which follow the concepts in a class of informal models developed to account for the striking dependence on the receptor type of several features of the calcium oscillations, in particular the shape and duration of the free calcium transients. The essence of these models is that the transients should be timed by a build-up of activated GTP-binding proteins, which, combined with positive feedback processes and perhaps with cooperative effects, leads to a sudden activation of phospholipase C (PLC), followed by negative feedback processes which switch off the calcium rise and lead to a fall in free calcium back to resting levels. These models predict pulsatile oscillations in inositol (1,4,5)P3 as well as in free calcium. We show that receptor-controlled intracellular calcium oscillators involving an unknown positive feedback pathway onto PLC and negative feedback from protein kinase C (PKC) onto G-proteins and receptors, or negative feedback by stimulation of GTPase activity can stimulate many of the features of observed intracellular calcium oscillations. These oscillators exhibit a dependence of frequency on agonist concentration and a dependence of transient duration on receptor and G-protein type. We also show that a PLC-dependent GTPase activating factor (GAF) could provide explanations for some otherwise puzzling features of intracellular calcium oscillations.