Hi-Fi transmission of periodic signals amid cell-to-cell variability.
Hi-Fi transmission of periodic signals amid cell-to-cell variability.
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DOI：
10.1039/c1mb05031a
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发表时间：
2011-07
影响因子：
--
通讯作者：
Takayama S
中科院分区：
文献类型：
--
作者：
Jovic A;Wade SM;Miyawaki A;Neubig RR;Linderman JJ;Takayama S
由于细胞内钙信号中的信息通常是频率编码的，因此找到可靠、方便和非侵入性的方法来携带它在生理上和实验上都是至关重要的。由于细胞间的可变性，在一群基因相同的细胞中，细胞内信号的同步仍然很难实现。对于内在振荡信号通路，如钙，在持续刺激下，细胞间的可变性表现为细胞内反应频率的差异。即使使用周期性刺激的携带，细胞间的差异性表现为细胞外输入转化为细胞内信号的保真度的差异。在这里，我们提出了一个理论和实验相结合的分析，展示了如何适当地平衡刺激强度，持续时间和休息间隔，以实现高保真的刺激-反应比的夹带g蛋白偶联受体触发的细胞内钙振荡。我们进一步证明，在细胞内酶水平和细胞表面受体水平的变化中，给予高保真携带的刺激参数显着改变。理论分析表明，在关键阈值下，即使这些蛋白质浓度或活性的微小变化也会导致夹带保真度的急剧变化，从而影响病理生理学。
Since information in intracellular calcium signaling is often frequency encoded, it is physiologically critical and experimentally useful to have reliable, convenient, and non-invasive methods to entrain it. Because of cell-to-cell variability, synchronization of intracellular signaling across a population of genetically identical cells can still be difficult to achieve. For intrinsically oscillatory signaling pathways, such as calcium, upon continuous stimulation, cell-to-cell variability is manifested as differences in intracellular response frequencies. Even with entrainment using periodic stimulation, cell-to-cell variability is manifested as differences in the fidelity with which extracellular inputs are converted into intracellular signals. Here we present a combined theoretical and experimental analysis that shows how to appropriately balance stimulation strength, duration, and rest intervals to achieve entrainment with high fidelity stimulation-to-response ratios for G-protein-coupled receptor-triggered intracellular calcium oscillations. We further demonstrate that stimulation parameters that give high fidelity entrainment are significantly altered upon changes in intracellular enzyme levels and cell surface receptor levels. Theoretical analysis suggests that, at key threshold values, even small changes in these protein concentrations or activities can results in precipitous changes in entrainment fidelity, with implications for pathophysiology.
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影响因子：
4.3
作者：
Jovic A;Howell B;Cote M;Wade SM;Mehta K;Miyawaki A;Neubig RR;Linderman JJ;Takayama S
通讯作者：
Takayama S
影响因子：
30.8
作者：
Lahav, G;Rosenfeld, N;Alon, U
通讯作者：
Alon, U
影响因子：
64.5
作者：
Altschuler SJ;Wu LF
通讯作者：
Wu LF
影响因子：
4.3
作者：
Kinzer-Ursem TL;Linderman JJ
通讯作者：
Linderman JJ
影响因子：
3.4
作者：
Fendler, B.;Zhang, M.;Bertram, R.
通讯作者：
Bertram, R.