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Issue 7, 2011
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Hi-Fi transmission of periodic signals amid cell-to-cell variability

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Abstract

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 result in precipitous changes in entrainment fidelity, with implications for pathophysiology.

Graphical abstract: Hi-Fi transmission of periodic signals amid cell-to-cell variability

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Supplementary files

Article information


Submitted
25 Jan 2011
Accepted
13 Apr 2011
First published
11 May 2011

Mol. BioSyst., 2011,7, 2238-2244
Article type
Paper

Hi-Fi transmission of periodic signals amid cell-to-cell variability

A. Jovic, S. M. Wade, A. Miyawaki, R. R. Neubig, J. J. Linderman and S. Takayama, Mol. BioSyst., 2011, 7, 2238
DOI: 10.1039/C1MB05031A

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