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

Wilson C, Saunter CD, Girkin JM, McCarron JG - FASEB J. (2016)

Bottom Line: D., Girkin, J.M., McCarron, J.Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium.

View Article: PubMed Central - PubMed

Affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; and.

No MeSH data available.


Related in: MedlinePlus

Multicellular signaling macrodomains (receptive field) provide high-sensitivity, wide dynamic-range agonist sensing in the vascular endothelium. Clusters of cells positioned close to each other have various sensitivities to ACh. As the ACh concentration increases (A), the most-sensitive cells activate first. (B, C). Less-sensitive cells (blue, green) activate at higher ACh concentrations. Over their sensitivity range, each cell responds with an ACh-concentration-dependent increase in [Ca2+]c (B, C). The combined activity of each of the cells provides the overall response of the endothelium (C, black line) and a high-sensitivity response over a wide concentration range.
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Figure 9: Multicellular signaling macrodomains (receptive field) provide high-sensitivity, wide dynamic-range agonist sensing in the vascular endothelium. Clusters of cells positioned close to each other have various sensitivities to ACh. As the ACh concentration increases (A), the most-sensitive cells activate first. (B, C). Less-sensitive cells (blue, green) activate at higher ACh concentrations. Over their sensitivity range, each cell responds with an ACh-concentration-dependent increase in [Ca2+]c (B, C). The combined activity of each of the cells provides the overall response of the endothelium (C, black line) and a high-sensitivity response over a wide concentration range.

Mentions: The environment in which the endothelium operates is a confusion of multiple agonists whose concentrations change almost continuously. Yet the endothelium sensitively discriminates very small changes in agonist concentration while being able to exclude random noise. The endothelium also provides responses that span a wide concentration range. How these normally incompatible detection features (insensitivity to noise, high sensitivity to signal, wide concentration sensitivity range) are reconciled and achieved is not well understood. Our results from large areas (∼200 cells) of endothelium in intact, pressurized arteries show the endothelium achieves high sensitivity, robustness to noise, and wide concentration range detection by integration of populationwide heterogeneous responses. Individual cells contribute only a small aspect of the overall features of detection. Each cell responded to chemical activation (ACh) with concentration-dependent increases in Ca2+ activity that spanned a single order of agonist-concentration magnitude. Intercellular variation in EC50 values (3 orders of magnitude) increased the bandwidth of concentration sensitivity and enabled collective endothelial responses to both low- and high-intensity stimuli. Cells with comparable sensitivity clustered in restricted spatial domains. This clustering acted as a noise rejection system by acting as a “coincidence detector.” Simultaneously activating several cells in the clusters triggered Ca2+ signals that transmitted to neighboring cells in a manner that scaled with stimulus intensity (Fig. 9). Thus, cell clustering and signal propagation provide an integrative mechanism for robust noise filtering and agonist sensing.


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

Wilson C, Saunter CD, Girkin JM, McCarron JG - FASEB J. (2016)

Multicellular signaling macrodomains (receptive field) provide high-sensitivity, wide dynamic-range agonist sensing in the vascular endothelium. Clusters of cells positioned close to each other have various sensitivities to ACh. As the ACh concentration increases (A), the most-sensitive cells activate first. (B, C). Less-sensitive cells (blue, green) activate at higher ACh concentrations. Over their sensitivity range, each cell responds with an ACh-concentration-dependent increase in [Ca2+]c (B, C). The combined activity of each of the cells provides the overall response of the endothelium (C, black line) and a high-sensitivity response over a wide concentration range.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4836367&req=5

Figure 9: Multicellular signaling macrodomains (receptive field) provide high-sensitivity, wide dynamic-range agonist sensing in the vascular endothelium. Clusters of cells positioned close to each other have various sensitivities to ACh. As the ACh concentration increases (A), the most-sensitive cells activate first. (B, C). Less-sensitive cells (blue, green) activate at higher ACh concentrations. Over their sensitivity range, each cell responds with an ACh-concentration-dependent increase in [Ca2+]c (B, C). The combined activity of each of the cells provides the overall response of the endothelium (C, black line) and a high-sensitivity response over a wide concentration range.
Mentions: The environment in which the endothelium operates is a confusion of multiple agonists whose concentrations change almost continuously. Yet the endothelium sensitively discriminates very small changes in agonist concentration while being able to exclude random noise. The endothelium also provides responses that span a wide concentration range. How these normally incompatible detection features (insensitivity to noise, high sensitivity to signal, wide concentration sensitivity range) are reconciled and achieved is not well understood. Our results from large areas (∼200 cells) of endothelium in intact, pressurized arteries show the endothelium achieves high sensitivity, robustness to noise, and wide concentration range detection by integration of populationwide heterogeneous responses. Individual cells contribute only a small aspect of the overall features of detection. Each cell responded to chemical activation (ACh) with concentration-dependent increases in Ca2+ activity that spanned a single order of agonist-concentration magnitude. Intercellular variation in EC50 values (3 orders of magnitude) increased the bandwidth of concentration sensitivity and enabled collective endothelial responses to both low- and high-intensity stimuli. Cells with comparable sensitivity clustered in restricted spatial domains. This clustering acted as a noise rejection system by acting as a “coincidence detector.” Simultaneously activating several cells in the clusters triggered Ca2+ signals that transmitted to neighboring cells in a manner that scaled with stimulus intensity (Fig. 9). Thus, cell clustering and signal propagation provide an integrative mechanism for robust noise filtering and agonist sensing.

Bottom Line: D., Girkin, J.M., McCarron, J.Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium.

View Article: PubMed Central - PubMed

Affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; and.

No MeSH data available.


Related in: MedlinePlus