A mathematical model of calcium dynamics in HSY cells.
A mathematical model of calcium dynamics in HSY cells.
复制标题
DOI：
10.1371/journal.pcbi.1005275
复制
发表时间：
2017-02
影响因子：
4.3
通讯作者：
Sneyd J
中科院分区：
文献类型：
--
作者：
Han JM;Tanimura A;Kirk V;Sneyd J
唾液是说话、咀嚼和吞咽等活动的重要组成部分。唾液中的酶可以保护牙齿和牙龈免受传染病的侵害，也可以启动消化过程。细胞内钙（Ca2+）在唾液分泌和调节中起关键作用。人类唾液管细胞系HSY细胞中Ca2+和肌醇三磷酸（IP3）浓度的实验测量表明，当细胞受到三磷酸腺苷（ATP）或碳醇（CCh）刺激时，它们表现出Ca2+峰值在IP3峰值之前的耦合振荡。基于这些数据，我们构建了HSY细胞中耦合Ca2+和IP3振荡的数学模型，并进行了三种不同实验设置的模型模拟来预测Ca2+响应。该模型预测，当Ca2+从细胞外空间内流被移除时，振荡逐渐减慢，直到它们停止。应用IP3脉冲的模型模拟预测，笼状IP3光解引起Ca2+振荡频率的瞬态增加。最后，当Ca2+依赖的PLC激活被抑制时，我们看到振荡频率的增加和幅度的减少。这些模型预测得到了实验数据的证实。我们得出结论，尽管Ca2+和IP3的浓度振荡，HSY细胞中的Ca2+振荡是细胞内Ca2+调节IP3受体的结果，并且该周期是由伴随的IP3振荡调节的。我们在人腮腺唾液导管细胞系HSY细胞中构建了Ca2+和IP3振荡的数学模型。该模型再现了实验数据，显示出[Ca2+]和[IP3]的耦合振荡，每个Ca2+峰值随后是IP3峰值。最近，人们推测HSY细胞中的IP3振荡并不是Ca2+振荡所必需的。我们用我们的模型证实了这一说法，并表明Ca2+振荡可以在没有振荡的情况下发生[IP3]。此外，基于我们的模型模拟，我们假设HSY细胞中的IP3振荡可能会影响Ca2+振荡的频率。事实上，实验数据证实振荡[IP3]延长了Ca2+振荡的周期。
Saliva is an essential part of activities such as speaking, masticating and swallowing. Enzymes in salivary fluid protect teeth and gums from infectious diseases, and also initiate the digestion process. Intracellular calcium (Ca2+) plays a critical role in saliva secretion and regulation. Experimental measurements of Ca2+ and inositol trisphosphate (IP3) concentrations in HSY cells, a human salivary duct cell line, show that when the cells are stimulated with adenosine triphosphate (ATP) or carbachol (CCh), they exhibit coupled oscillations with Ca2+ spike peaks preceding IP3 spike peaks. Based on these data, we construct a mathematical model of coupled Ca2+ and IP3 oscillations in HSY cells and perform model simulations of three different experimental settings to forecast Ca2+ responses. The model predicts that when Ca2+ influx from the extracellular space is removed, oscillations gradually slow down until they stop. The model simulation of applying a pulse of IP3 predicts that photolysis of caged IP3 causes a transient increase in the frequency of the Ca2+ oscillations. Lastly, when Ca2+-dependent activation of PLC is inhibited, we see an increase in the oscillation frequency and a decrease in the amplitude. These model predictions are confirmed by experimental data. We conclude that, although concentrations of Ca2+ and IP3 oscillate, Ca2+ oscillations in HSY cells are the result of modulation of the IP3 receptor by intracellular Ca2+, and that the period is modulated by the accompanying IP3 oscillations. We construct a mathematical model of Ca2+ and IP3 oscillations in HSY cells, a salivary ductal cell line from human parotid. The model reproduces the experimental data that exhibit coupled oscillations of [Ca2+] and [IP3] with the peak of each Ca2+ spike being followed by the peak of an IP3 spike. Recently, it was conjectured that IP3 oscillations in HSY cells are not necessary for Ca2+ oscillations. We corroborate this statement with our model and show that Ca2+ oscillations can occur without oscillating [IP3]. Further to this, based on our model simulation, we hypothesise that IP3 oscillations in HSY cells may affect the frequency of Ca2+ oscillations. Indeed, experimental data verify that oscillating [IP3] lengthens the period of Ca2+ oscillations.