缺乏 SOCE 的 HEK293 细胞中的钙振荡表明 IP3 的产生和降解存在平衡调控

Clara Octors, Ryan E. Yoast, Scott M. Emrich, Mohamed Trebak, James Sneyd
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摘要

细胞膜游离 Ca2+ 的浓度是几乎所有细胞类型中的关键第二信使,其信号通常由细胞膜 Ca2+ 浓度的振荡周期或尖峰传递。我们以前曾研究过质膜上的 Ca2+ 流入如何影响 HEK293 细胞中 Ca2+ 振荡的周期和形状。然而,我们的理论工作无法解释 Ca2+ 振荡的形状如何在单个时间序列的过程中发生质的变化,从细尖峰到宽振荡。振荡形状的这种质变是 STIM1 和 2 被敲除的 HEK293 细胞的共同特征。在这里,我们提出了一个早期模型的扩展版本,该模型认为振荡形状的这种随时间变化的质变可能是 Ca2+ 对三磷酸肌醇的产生和降解的正负反馈平衡的结果。
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Calcium oscillations in HEK293 cells lacking SOCE suggest the existence of a balanced regulation of IP3 production and degradation
The concentration of free cytosolic Ca2+ is a critical second messenger in almost every cell type, with the signal often being carried by the period of oscillations, or spikes, in the cytosolic Ca2+ concentration. We have previously studied how Ca2+ influx across the plasma membrane affects the period and shape of Ca2+ oscillations in HEK293 cells. However, our theoretical work was unable to explain how the shape of Ca2+ oscillations could change qualitatively, from thin spikes to broad oscillations, during the course of a single time series. Such qualitative changes in oscillation shape are a common feature of HEK293 cells in which STIM1 and 2 have been knocked out. Here, we present an extended version of our earlier model that suggests that such time-dependent qualitative changes in oscillation shape might be the result of balanced positive and negative feedback from Ca2+ to the production and degradation of inositol trisphosphate.
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