title: Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium.
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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; and.
authors.forename: Calum
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Centre for Advanced Instrumentation, Biophysical Sciences Institute, Department of Physics, Durham University, Durham, United Kingdom.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Saunter
authors.affiliation: Centre for Advanced Instrumentation, Biophysical Sciences Institute, Department of Physics, Durham University, Durham, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Girkin
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; and john.mccarron@strath.ac.uk.
authors.forename: John G
authors.initials: JG
authors.lastname: McCarron
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000109:Acetylcholine
keywords: calcium imaging; endothelial calcium signalling; endothelial heterogeneity; gradient index; microendoscopy