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.

doi:10.1096/fj.201500090

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.

Authors

Calum Wilson

Christopher D. Saunter

Professor John Girkin j.m.girkin@durham.ac.uk
Professor

John G. McCarron

Abstract

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.

Citation

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
Journal	FASEB Journal
Print ISSN	0892-6638
Electronic ISSN	1530-6860
Publisher	Federation of American Society of Experimental Biology (FASEB)
Peer Reviewed	Peer Reviewed
Volume	30
Issue	5
Pages	2000-2013
DOI	https://doi.org/10.1096/fj.201500090
Keywords	Endothelial calcium signalling, Microendoscopy, Gradient index, Calcium imaging, Endothelial heterogeneity.

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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.