A SINGLE-POOL INOSITOL 1,4,5-TRISPHOSPHATE-RECEPTOR-BASED MODEL FOR AGONIST-STIMULATED OSCILLATIONS IN CA2+ CONCENTRATION
A SINGLE-POOL INOSITOL 1,4,5-TRISPHOSPHATE-RECEPTOR-BASED MODEL FOR AGONIST-STIMULATED OSCILLATIONS IN CA2+ CONCENTRATION
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DOI：
10.1073/pnas.89.20.9895
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发表时间：
1992-10-15
影响因子：
11.1
通讯作者：
KEIZER, J
中科院分区：
文献类型：
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作者：
DEYOUNG, GW;KEIZER, J
依赖于定量测量的Ca 2+激活和抑制的肌醇1，4，5-三磷酸（IP 3）受体在内质网中，我们构建了一个简化的动力学模型来描述这个通道的属性。选择速率常数来拟合关键的动力学和平衡数据，我们发现该模型重现了各种体内和体外实验。结合Ca 2 +-ATP酶活性的Ca 2+摄取到内质网中，该模型导致在固定的IP 3浓度和只有一个池的可释放的Ca 2+，内质网的Ca 2+浓度的细胞质振荡。磷脂酶C对Ca 2+产生IP 3的正反馈机制的引入丰富了振荡的性质，并导致Ca 2+浓度振荡伴随IP 3浓度振荡。我们讨论了这些结果的解释实验的可能意义。
Relying on quantitative measurements of Ca2+ activation and inhibition of the inositol 1,4,5-trisphosphate (IP3) receptor in the endoplasmic reticulum, we construct a simplified kinetic model to describe the properties of this channel. Selecting rate constants to fit key kinetic and equilibrium data, we find that the model reproduces a variety of in vivo and in vitro experiments. In combination with Ca2+-ATPase activity for Ca2+ uptake into the endoplasmic reticulum, the model leads to cytoplasmic oscillations in Ca2+ concentration at fixed IP3 concentration and only a single pool of releasable Ca2+, the endoplasmic reticulum. Incorporation of a positive-feedback mechanism of Ca2+ on IP3 production by phospholipase C enriches the properties of the oscillations and leads to oscillations in Ca2+ concentration accompanied by oscillations in IP3 concentration. We discuss the possible significance of these results for the interpretation of experiments.