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通过肌醇三磷酸受体簇对钙离子释放进行缓冲调节的建模。

Modeling of the modulation by buffers of Ca2+ release through clusters of IP3 receptors.

作者信息

Zeller S, Rüdiger S, Engel H, Sneyd J, Warnecke G, Parker I, Falcke M

机构信息

Institute for Theoretical Physics, Technische Universität Berlin, Berlin, Germany.

出版信息

Biophys J. 2009 Aug 19;97(4):992-1002. doi: 10.1016/j.bpj.2009.05.050.

DOI:10.1016/j.bpj.2009.05.050
PMID:19686646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2726323/
Abstract

Intracellular Ca(2+) release is a versatile second messenger system. It is modeled here by reaction-diffusion equations for the free Ca(2+) and Ca(2+) buffers, with spatially discrete clusters of stochastic IP(3) receptor channels (IP(3)Rs) controlling the release of Ca(2+) from the endoplasmic reticulum. IP(3)Rs are activated by a small rise of the cytosolic Ca(2+) concentration and inhibited by large concentrations. Buffering of cytosolic Ca(2+) shapes global Ca(2+) transients. Here we use a model to investigate the effect of buffers with slow and fast reaction rates on single release spikes. We find that, depending on their diffusion coefficient, fast buffers can either decouple clusters or delay inhibition. Slow buffers have little effect on Ca(2+) release, but affect the time course of the signals from the fluorescent Ca(2+) indicator mainly by competing for Ca(2+). At low [IP(3)], fast buffers suppress fluorescence signals, slow buffers increase the contrast between bulk signals and signals at open clusters, and large concentrations of buffers, either fast or slow, decouple clusters.

摘要

细胞内Ca(2+)释放是一种多功能的第二信使系统。在此通过自由Ca(2+)和Ca(2+)缓冲剂的反应扩散方程对其进行建模,具有空间离散的随机IP(3)受体通道(IP(3)Rs)簇控制内质网中Ca(2+)的释放。IP(3)Rs由胞质Ca(2+)浓度的小幅升高激活,并被高浓度抑制。胞质Ca(2+)的缓冲作用塑造了整体Ca(2+)瞬变。在这里,我们使用一个模型来研究具有慢反应速率和快反应速率的缓冲剂对单个释放尖峰的影响。我们发现,根据其扩散系数,快速缓冲剂既可以使簇解耦,也可以延迟抑制。慢速缓冲剂对Ca(2+)释放影响很小,但主要通过竞争Ca(2+)来影响来自荧光Ca(2+)指示剂的信号的时间进程。在低[IP(3)]时,快速缓冲剂抑制荧光信号,慢速缓冲剂增加整体信号与开放簇处信号之间的对比度,而高浓度的缓冲剂,无论是快速还是慢速,都会使簇解耦。

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