Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium
Wilson, Calum; Saunter, Christopher D.; Girkin, John M.; McCarron, John G.
Christopher D. Saunter
Professor John Girkin email@example.com
John G. McCarron
Agonist-mediated signaling by the endothelium controls virtually all vascular functions. Because of the large diversity of agonists, each with varying concentrations, background noise often obscures individual cellular signals. How the endothelium distinguishes low-level fluctuations from noise and decodes and integrates physiologically relevant information remains unclear. Here, we recorded changes in intracellular Ca2+ concentrations in response to acetylcholine in areas encompassing hundreds of endothelial cells from inside intact pressurized arteries. Individual cells responded to acetylcholine with a concentration-dependent increase in Ca2+ signals spanning a single order of magnitude. Interestingly, however, intercellular response variation extended over 3 orders of magnitude of agonist concentration, thus crucially enhancing the collective bandwidth of endothelial responses to agonists. We also show the accuracy of this collective mode of detection is facilitated by spatially restricted clusters of comparably sensitive cells arising from heterogeneous receptor expression. Simultaneous stimulation of clusters triggered Ca2+ signals that were transmitted to neighboring cells in a manner that scaled with agonist concentration. Thus, the endothelium detects agonists by acting as a distributed sensing system. Specialized clusters of detector cells, analogous to relay nodes in modern communication networks, integrate populationwide inputs, and enable robust noise filtering for efficient high-fidelity signaling.—Wilson, C., Saunter, C. D., Girkin, J. M., McCarron, J. G. Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium.
Wilson, C., Saunter, C. D., Girkin, J. M., & McCarron, J. G. (2016). Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium. FASEB Journal, 30(5), 2000-2013. https://doi.org/10.1096/fj.201500090
|Journal Article Type||Article|
|Acceptance Date||Jan 27, 2016|
|Online Publication Date||Feb 12, 2016|
|Publication Date||May 1, 2016|
|Deposit Date||Feb 17, 2016|
|Publicly Available Date||Feb 17, 2016|
|Publisher||Federation of American Society of Experimental Biology (FASEB)|
|Peer Reviewed||Peer Reviewed|
|Keywords||Endothelial calcium signalling, Microendoscopy, Gradient index, Calcium imaging, Endothelial heterogeneity.|
Published Journal Article (Advance online version)
Publisher Licence URL
Advance online version © The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Published Journal Article (Final published version)
Publisher Licence URL
Final published version
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