Department of Neurobiology & Behavior, UC Irvine, Irvine, United States.
Department of Physiology & Biophysics, UC Irvine, Irvine, United States.
Elife. 2020 May 12;9:e55008. doi: 10.7554/eLife.55008.
The 'building-block' model of inositol trisphosphate (IP)-mediated Ca liberation posits that cell-wide cytosolic Ca signals arise through coordinated activation of localized Ca puffs generated by stationary clusters of IP receptors (IPRs). Here, we revise this hypothesis, applying fluctuation analysis to resolve Ca signals otherwise obscured during large Ca elevations. We find the rising phase of global Ca signals is punctuated by a flurry of puffs, which terminate before the peak by a mechanism involving partial ER Ca depletion. The continuing rise in Ca, and persistence of global signals even when puffs are absent, reveal a second mode of spatiotemporally diffuse Ca signaling. Puffs make only small, transient contributions to global Ca signals, which are sustained by diffuse release of Ca through a functionally distinct process. These two modes of IP-mediated Ca liberation have important implications for downstream signaling, imparting spatial and kinetic specificity to Ca-dependent effector functions and Ca transport.
三磷酸肌醇（IP）介导的 Ca 释放的“积木”模型假设，通过协调局部 Ca 爆发的激活，产生细胞范围的细胞质 Ca 信号，这些局部 Ca 爆发由静止的 IP 受体（IPR）簇产生。在这里，我们修正了这个假设，应用波动分析来解决在大 Ca 升高期间被掩盖的 Ca 信号。我们发现，全局 Ca 信号的上升阶段被一连串的爆发所打断，这些爆发通过一种涉及内质网 Ca 耗竭部分的机制，在峰值之前终止。Ca 的持续上升，以及在没有爆发时全局信号的持续存在，揭示了一种具有时空弥散特征的第二种 Ca 信号传递模式。爆发只对全局 Ca 信号做出微小的、短暂的贡献，而全局信号的持续则是通过一种功能上不同的过程通过弥散释放 Ca 来维持的。这两种 IP 介导的 Ca 释放模式对下游信号传递具有重要意义，为 Ca 依赖性效应功能和 Ca 转运赋予了空间和动力学特异性。
