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Published October 20, 2010 | public
Journal Article

Variability in G-Protein-Coupled Signaling Studied with Microfluidic Devices


Different cells, even those that are genetically identical, can respond differently to identical stimuli, but the precise source of this variability remains obscure. To study this problem, we built a microfluidic experimental system which can track responses of individual cells across multiple stimulations. We used this system to determine that amplitude variation in G-protein-activated calcium release in RAW264.7 macrophages is generally extrinsic, i.e., they arise from long-lived variations between cells and not from stochastic activation of signaling components. In the case of responses linked to P2Y family purine receptors, we estimate that approximately one-third of the observed variability in calcium release is receptor-specific. We further demonstrate that the signaling apparatus downstream of P2Y6 receptor activation is moderately saturable. These observations will be useful in constructing and constraining single-cell models of G protein-coupled calcium dynamics.

Additional Information

© 2010 Biophysical Society; Published by Elsevier Inc. Received 3 November 2009; accepted 24 August 2010. Editor: Andre Levchenko. Available online 19 October 2010. We thank members of the Simon laboratory for excellent technical assistance; and T. Squires, M. Diehl, M. Baym, D. Zhang, an anonymous referee, and members of the Quake group and the Alliance for Cell Signaling for helpful comments. This work was funded in part by the National Institute of General Medical Sciences Glue Grant Initiative (No. U54 GM062114), and by a Senior Scholar award in Aging from the Ellison Medical Foundation to M.I.S. X.R.B. acknowledges support from the Fannie and John Hertz Foundation.

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August 19, 2023
October 20, 2023