《厦门大学学报（自然科学版）》

细胞质钙离子(Ca2+)常以浓度振荡变化的方式控制许多生理活动,内质网上的三磷酸肌醇受体(inositol 1,4,5-trisphosphate receptor,IP3R)通道是产生钙振荡的关键因素,因此研究其振荡机制具有重要意义.虽然钙振荡已被广泛建模,但大部分模型细胞质与内质网中钙振荡的范围与实验观测数据差异较大.通过整合最近的实验结果,基于IP3R通道活性对细胞质Ca2+浓度依赖的钟型曲线构建了一个新的钙振荡模型.模型结果除了可以很好地模拟实验中关于钙振荡范围的数据,还可重复多种实验现象.对模型进行参数敏感性分析后,进一步采用单参数分岔分析分别研究了两个高敏感参数,即细胞质内Ca2+缓冲蛋白的总浓度和IP3R通道激活Ca2+的解离常数(K1)对钙振荡的影响,发现它们对钙信号有相反的作用.对三磷酸肌醇(IP3)浓度和K1进行双参数分岔分析的结果表明K1对IP3能产生钙振荡的区域及其振幅有重要影响,揭示可以通过改变K1影响细胞对外界刺激的响应及其钙振荡模式.该研究有助于理解钙振荡机制,并可为后续理论研究提供框架.

Oscillations in cytosolic calcium concentration(cCa_Cyt)regulate a diverse range of cellular processes.Dynamic properties of inositol 1,4,5-trisphosphate receptor(IP3R)located on the endoplasmic reticulum are crucial for the generation of Ca2+ oscillations.Thus,it is of great interest to determine mechanisms governing such oscillations.Although Ca2+ oscillations have been modeled extensively,one major problem with almost all published models lies in that the oscillatory ranges of cCa_Cyt and calcium concentration in endoplasmic reticulum(cCa_ER)do not agree with recent experimental data.By integrating recent experimental results,a new calcium oscillation model is constructed based on bell-shaped dependence of IP3R gating on cCa_Cyt.The cCa_Cyt and cCa_ER obtained by the model lie in ranges of experimental results.In addition,the model can successfully reproduce several features described in experimental studies.After parameter sensitivity analysis of the model,the single-parameter bifurcation analysis is conducted to study the impact of two high-sensitivity parameters,i.e.,the total concentration of cytoplasmic Ca2+ binding protein and IP3R dissociation constant for activating Ca2+(K1)on Ca2+ oscillations. Results suggest that they exert an opposite effect on calcium signal.The result of two-parameter bifurcation analysis of IP3 concentration and K1 indicates that K1 plays a crucial role on the region of IP3 concentration that can generate Ca2+ oscillations and their amplitudes,revealing that K1 can affect the response of cells to external stimuli and the Ca2+ oscillatory pattern of the cells.This study not only helps to understand the mechanism of Ca2+ oscillations,but also provides a framework for subsequent theoretical research.

引言
1 模型与方法
2 结果与分析
3 结论

图1 钙振荡机制图<br/>Fig.1 Mechanism diagram of calcium oscillation

图1 钙振荡机制图
Fig.1 Mechanism diagram of calcium oscillation

图2 IP3R通道的动力学<br/>Fig.2 Dynamics of IP3R channel

图2 IP3R通道的动力学
Fig.2 Dynamics of IP3R channel

表1 模型中的参数<br/>Tab.1 Parameters in the model

表1 模型中的参数
Tab.1 Parameters in the model

图3 IP3R通道的开放概率<br/>Fig.3 popen of IP3R channel

图3 IP3R通道的开放概率
Fig.3 popen of IP3R channel

图4 标准参数下钙振荡模型的时间序列和分岔分析<br/>Fig.4 Time series and bifurcation analysis of calcium oscillation model under standard parameters

图4 标准参数下钙振荡模型的时间序列和分岔分析
Fig.4 Time series and bifurcation analysis of calcium oscillation model under standard parameters

图5 参数改变±10%时的参数敏感性分析<br/>Fig.5 Parameter sensitivity analysis when the parameters change±10%(a)cB_T对cCa_Cyt的分岔图;(b)K1对cCa_Cyt的分岔图.

图5 参数改变±10%时的参数敏感性分析
Fig.5 Parameter sensitivity analysis when the parameters change±10%(a)cB_T对cCa_Cyt的分岔图;(b)K1对cCa_Cyt的分岔图.

图6 单参数分岔图<br/>Fig.6 The one-parameter bifurcation diagram

图6 单参数分岔图
Fig.6 The one-parameter bifurcation diagram

图7 标准参数下的双参数分岔图以及另一组参数下的分岔分析<br/>Fig.7 Two-parameter bifurcation diagram under standard parameters and bifurcation analysis under another set of parameters

图7 标准参数下的双参数分岔图以及另一组参数下的分岔分析
Fig.7 Two-parameter bifurcation diagram under standard parameters and bifurcation analysis under another set of parameters

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引言

1 模型与方法

2 结果与分析

3 结论

学报简介

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引言

1 模型与方法

2 结果与分析

3 结 论

学报简介

3 结论