Cookies

We use cookies to ensure that we give you the best experience on our website. By continuing to browse this repository, you give consent for essential cookies to be used. You can read more about our Privacy and Cookie Policy.


Durham Research Online
You are in:

Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium.

Wilson, Calum and Saunter, Christopher D. and Girkin, John M. and McCarron, John G. (2016) 'Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium.', The FASEB journal., 30 (5). pp. 2000-2013.

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.

Item Type:Article
Keywords:Endothelial calcium signalling, Microendoscopy, Gradient index, Calcium imaging, Endothelial heterogeneity.
Full text:(VoR) Version of Record
Available under License - Creative Commons Attribution.
Download PDF (Advance online version)
(3042Kb)
Full text:(VoR) Version of Record
Available under License - Creative Commons Attribution.
Download PDF (Final published version)
(2992Kb)
Status:Peer-reviewed
Publisher Web site:http://dx.doi.org/10.1096/fj.201500090
Publisher statement:© 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.
Date accepted:27 January 2016
Date deposited:17 February 2016
Date of first online publication:12 February 2016
Date first made open access:No date available

Save or Share this output

Export:
Export
Look up in GoogleScholar