Timescales of IP3-Evoked Ca2+ Spikes Emerge from Ca2+ Puffs Only at the Cellular Level

Timescales of IP3-Evoked Ca2+ Spikes Emerge from Ca2+ Puffs Only at the Cellular Level
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DOI:
10.1016/j.bpj.2011.10.030
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发表时间:
2011-12-07
影响因子:
3.4
通讯作者:
Falcke, Martin
Falcke, Martin
中科院分区:
生物学3区
文献类型:
--
作者:
Thurley, Kevin;Smith, Ian F.;Falcke, Martin

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生物系统的行为由其组成分子的性质决定,但相互作用通常过于复杂,无法完全理解分子行为如何产生细胞行为。三磷酸肌醇受体(IP3R)的Ca2+信号提供了一个机会,以了解这种关系,因为细胞行为主要是由Ca2+介导的IP3R之间的相互作用。由IP3R簇释放的Ca2+(给出局部Ca2+喷流)扩散并点燃相邻簇的行为(以给出重复的全局Ca2+尖峰)。我们使用全内反射荧光显微镜的两个哺乳动物细胞系,以定义之间的时间关系的Ca2+泡芙(interpuff间隔,IPI)和Ca2+尖峰(interspike间隔)引起的闪光光解笼IP3。我们发现,IPI是远远短于interspike间隔,即泡芙活动是随机的恢复时间,这是远远短于细胞的不应期,IPI是不是周期性的。我们的结论是,Ca2+尖峰不产生振荡动力学的IP3R集群,但重复的Ca2+尖峰与其较长的时间尺度是一个新兴的属性的动态的整个集群阵列。
The behavior of biological systems is determined by the properties of their component molecules, but the interactions are usually too complex to understand fully how molecular behavior generates cellular behavior. Ca2+ signaling by inositol trisphosphate receptors (IP3R) offers an opportunity to understand this relationship because the cellular behavior is defined largely by Ca2+-mediated interactions between IP3R. Ca2+ released by a cluster of IP3R (giving a local Ca2+ puff) diffuses and ignites the behavior of neighboring clusters (to give repetitive global Ca2+ spikes). We use total internal reflection fluorescence microscopy of two mammalian cell lines to define the temporal relationships between Ca2+ puffs (interpuff intervals, IPI) and Ca2+ spikes (interspike intervals) evoked by flash photolysis of caged IP3. We find that IPI are much shorter than interspike intervals, that puff activity is stochastic with a recovery time that is much shorter than the refractory period of the cell, and that IPI are not periodic. We conclude that Ca2+ spikes do not arise from oscillatory dynamics of IP3R clusters, but that repetitive Ca2+ spiking with its longer timescales is an emergent property of the dynamics of the whole cluster array.