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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

Graded concentration responses to ACh. A–C) As the concentration of ACh increased, the number of cells activated increased. A, B) Maximum intensity projections show the total number of cells activated at 3µM (A) and 30 µM (B) ACh. As the concentration of ACh increases, more cells are activated. Scale bars, 100 μm. C) Summarized data showing number of active cells (EC50 = 18.9 μM; 95% confidence interval, 7.25–49.4 μM; n = 3). D) The amplitude of response in each cell also increased with concentration of ACh. The responses to 3 illustrative concentrations from the full concentration–response relationship are shown. The responses in each cell have been time-aligned and color-coded based on ACh sensitivity of the cells at the lowest ACh concentration: red, most sensitive; blue, least sensitive. As the concentration of ACh increases, the amplitude of the responses increases. There is overlap in the response between 30 and 300 μM because of the position in the concentration response relationship. E) Representative concentration responses from 4 cells in 1 experiment that show a range of sensitivities to increasing ACh concentration. F) Scatter plot of the overall responses from 445 cells from 3 arteries. The red dots plot the mean response at each concentration. The overall relationship appears flat because all responses at each concentration from separate arteries are shown. G) Total endothelial responses (EC50 = 42.7 μM; 95% confidence interval, 20.2–90.1 μM; n = 3) derived from the product of the number of active cells (C) and mean response (F) at each concentration.
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Figure 3: Graded concentration responses to ACh. A–C) As the concentration of ACh increased, the number of cells activated increased. A, B) Maximum intensity projections show the total number of cells activated at 3µM (A) and 30 µM (B) ACh. As the concentration of ACh increases, more cells are activated. Scale bars, 100 μm. C) Summarized data showing number of active cells (EC50 = 18.9 μM; 95% confidence interval, 7.25–49.4 μM; n = 3). D) The amplitude of response in each cell also increased with concentration of ACh. The responses to 3 illustrative concentrations from the full concentration–response relationship are shown. The responses in each cell have been time-aligned and color-coded based on ACh sensitivity of the cells at the lowest ACh concentration: red, most sensitive; blue, least sensitive. As the concentration of ACh increases, the amplitude of the responses increases. There is overlap in the response between 30 and 300 μM because of the position in the concentration response relationship. E) Representative concentration responses from 4 cells in 1 experiment that show a range of sensitivities to increasing ACh concentration. F) Scatter plot of the overall responses from 445 cells from 3 arteries. The red dots plot the mean response at each concentration. The overall relationship appears flat because all responses at each concentration from separate arteries are shown. G) Total endothelial responses (EC50 = 42.7 μM; 95% confidence interval, 20.2–90.1 μM; n = 3) derived from the product of the number of active cells (C) and mean response (F) at each concentration.

Mentions: Taking this approach, several unique features of the endothelium’s response to increasing concentration of ACh were now apparent (Fig. 3). First, at low concentrations only a small number of cells activated (sensitive cells; Fig. 3A and Supplemental Movie 2). As the agonist concentration increased, additional cells were recruited in a concentration-dependent manner (Fig. 3A–C and Supplemental Movie 2). Second, after recruitment, the amplitude of [Ca2+]c response within each cell also increased in a concentration-dependent manner (i.e., each cell responded with a typical concentration–response relationship) (Fig. 3D–F). However, individual cells operated over various concentration ranges (Fig. 3D, E). The overall response of the endothelium was derived from the combined, separate, concentration sensitivity of each cell of the population (Fig. 3G). Each cell’s responsewas constrained to <102 concentration (Fig. 3E), though the overall response of the endothelium was spread over 3 orders of magnitude of concentration (Fig. 3G). These results suggest that endothelial cells are primed with a limited range of sensitivity that varies significantly among cells. The combined activity determines the amplitude of Ca2+ response to provide a detection system with both high sensitivity and wide dynamic range.


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)

Graded concentration responses to ACh. A–C) As the concentration of ACh increased, the number of cells activated increased. A, B) Maximum intensity projections show the total number of cells activated at 3µM (A) and 30 µM (B) ACh. As the concentration of ACh increases, more cells are activated. Scale bars, 100 μm. C) Summarized data showing number of active cells (EC50 = 18.9 μM; 95% confidence interval, 7.25–49.4 μM; n = 3). D) The amplitude of response in each cell also increased with concentration of ACh. The responses to 3 illustrative concentrations from the full concentration–response relationship are shown. The responses in each cell have been time-aligned and color-coded based on ACh sensitivity of the cells at the lowest ACh concentration: red, most sensitive; blue, least sensitive. As the concentration of ACh increases, the amplitude of the responses increases. There is overlap in the response between 30 and 300 μM because of the position in the concentration response relationship. E) Representative concentration responses from 4 cells in 1 experiment that show a range of sensitivities to increasing ACh concentration. F) Scatter plot of the overall responses from 445 cells from 3 arteries. The red dots plot the mean response at each concentration. The overall relationship appears flat because all responses at each concentration from separate arteries are shown. G) Total endothelial responses (EC50 = 42.7 μM; 95% confidence interval, 20.2–90.1 μM; n = 3) derived from the product of the number of active cells (C) and mean response (F) at each concentration.
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Figure 3: Graded concentration responses to ACh. A–C) As the concentration of ACh increased, the number of cells activated increased. A, B) Maximum intensity projections show the total number of cells activated at 3µM (A) and 30 µM (B) ACh. As the concentration of ACh increases, more cells are activated. Scale bars, 100 μm. C) Summarized data showing number of active cells (EC50 = 18.9 μM; 95% confidence interval, 7.25–49.4 μM; n = 3). D) The amplitude of response in each cell also increased with concentration of ACh. The responses to 3 illustrative concentrations from the full concentration–response relationship are shown. The responses in each cell have been time-aligned and color-coded based on ACh sensitivity of the cells at the lowest ACh concentration: red, most sensitive; blue, least sensitive. As the concentration of ACh increases, the amplitude of the responses increases. There is overlap in the response between 30 and 300 μM because of the position in the concentration response relationship. E) Representative concentration responses from 4 cells in 1 experiment that show a range of sensitivities to increasing ACh concentration. F) Scatter plot of the overall responses from 445 cells from 3 arteries. The red dots plot the mean response at each concentration. The overall relationship appears flat because all responses at each concentration from separate arteries are shown. G) Total endothelial responses (EC50 = 42.7 μM; 95% confidence interval, 20.2–90.1 μM; n = 3) derived from the product of the number of active cells (C) and mean response (F) at each concentration.
Mentions: Taking this approach, several unique features of the endothelium’s response to increasing concentration of ACh were now apparent (Fig. 3). First, at low concentrations only a small number of cells activated (sensitive cells; Fig. 3A and Supplemental Movie 2). As the agonist concentration increased, additional cells were recruited in a concentration-dependent manner (Fig. 3A–C and Supplemental Movie 2). Second, after recruitment, the amplitude of [Ca2+]c response within each cell also increased in a concentration-dependent manner (i.e., each cell responded with a typical concentration–response relationship) (Fig. 3D–F). However, individual cells operated over various concentration ranges (Fig. 3D, E). The overall response of the endothelium was derived from the combined, separate, concentration sensitivity of each cell of the population (Fig. 3G). Each cell’s responsewas constrained to <102 concentration (Fig. 3E), though the overall response of the endothelium was spread over 3 orders of magnitude of concentration (Fig. 3G). These results suggest that endothelial cells are primed with a limited range of sensitivity that varies significantly among cells. The combined activity determines the amplitude of Ca2+ response to provide a detection system with both high sensitivity and wide dynamic range.

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