Spatial and temporal aspects of cellular calcium signaling
Spatial and temporal aspects of cellular calcium signaling
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DOI：
10.1096/fasebj.10.13.8940296
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发表时间：
1996-11-01
期刊：
影响因子：
4.8
通讯作者：
Putney, JW
中科院分区：
文献类型：
--
作者：
Thomas, AP;Bird, GSJ;Putney, JW
即使在持续刺激的条件下，细胞内的钙信号也经常以复杂的时间和空间模式组织起来。在这篇综述中，我们讨论了在不可兴奋的细胞中这一行为的机制和生理意义，其中钙动员的主要机制是通过(1，4，5)依赖于IP3的细胞内钙释放。细胞内游离钙的振荡([Ca~(2+)](I))是一种常见的时间组织形式；在空间域中，这些[Ca~(2+)](I)振荡可以采取[Ca~(2+)](I)波的形式传播到整个细胞，也可以限制在特定的亚细胞区域。这些Ca~(2+)信号模式是由于细胞质内Ca~(2+)扩散的有限范围和负责Ca~(2+)动员的通路的反馈调节所致。此外，[Ca~(2+)](I)变化的空间组织似乎取决于细胞内Ca~(2+)存储的战略分布。[Ca~(2+)](I)振荡的一种类型是基线尖峰，其中离散的[Ca~(2+)](I)尖峰的出现频率是由激动剂剂量决定的，而不是幅度。大多数现有证据支持一种模型，即基线[Ca~(2+)](I)尖峰是由于[Ca~(2+)](I)和(1，4，5)IP3在调节(1，4，5)IP3敏感的细胞内Ca~(2+)通道门控中的复杂相互作用而产生的。正弦[Ca~(2+)](I)振荡代表了一种不同的力学类型的时间组织，其中激动剂剂量调节幅度，但不影响振荡频率。蛋白激酶C在磷脂酶C或其激活G蛋白水平上对(1，4，5)IP3的产生产生负反馈作用可解释正弦[Ca~(2+)](I)振荡。随着对完整组织中这一行为的观察，以及对适应于频率调制的振荡信号的钙依赖过程的认识，[Ca~(2+)](I)振荡和波动的生理意义正变得更加确定。在一些细胞中，这些[Ca~(2+)](I)信号的目标是控制有限的细胞质区域中的过程，而在其他系统中，[Ca~(2+)](I)波可以通过缝隙连接传播，以协调多细胞系统的功能。
Cytosolic Ca2+ signals are often organized in complex temporal and spatial patterns, even under conditions of sustained stimulation. In this review we discuss the mechanisms and physiological significance of this behavior in nonexcitable cells, in which the primary mechanism of Ca2+ mobilization is through (1,4,5)IP3-dependent Ca2+ release from intracellular stores. Oscillations of cytosolic free Ca2+ ([Ca2+](i)) are a common form of temporal organization; in the spatial domain, these [Ca2+](i) oscillations may take the form of [Ca2+](i) waves that propagate throughout the cell or they may be restricted to specific subcellular regions. These patterns of Ca2+ signaling result from the limited range of cytoplasmic Ca2+ diffusion and the feedback regulation of the pathways responsible for Ca2+ mobilization. In addition, the spatial organization of [Ca2+](i) changes appears to depend on the strategic distribution of Ca2+ stores within the cell. One type of [Ca2+](i) oscillation is baseline spiking, in which discrete [Ca2+](i) spikes occur with a frequency, but not amplitude, that is determined by agonist dose. Most current evidence favors a model in which baseline [Ca2+](i) spiking results from the complex interplay between [Ca2+](i) and (1,4,5)IP3 in regulating the gating of (1,4,5)IP3-sensitive intracellular Ca2+ channels. Sinusoidal [Ca2+](i) oscillations represent a mechanistically distinct type of temporal organization, in which agonist dose regulates the amplitude but has no effect on oscillation frequency. Sinusoidal [Ca2+](i) oscillations can be explained by a negative feedback effect of protein kinase C on the generation of (1,4,5)IP3 at the level of phospholipase C or its activating G-protein. The physiological significance of [Ca2+](i) oscillations and waves is becoming more established with the observation of this behavior in intact tissues and by the recognition of Ca2+-dependent processes that are adapted to respond to frequency-modulated oscillatory [Ca2+](i) signals. In some cells, these [Ca2+](i) signals are targeted to control processes in limited cytoplasmic domains, and in other systems [Ca2+](i) waves can be propagated through gap junctions to coordinate the function of multicellular systems.