scholarly journals Transport-dependent calcium signaling in spatially segregated cellular caveolar domains

2008 ◽  
Vol 294 (3) ◽  
pp. C856-C866 ◽  
Author(s):  
Dihui Hong ◽  
Dov Jaron ◽  
Donald G. Buerk ◽  
Kenneth A. Barbee
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathways ◽  
Calcium Concentration ◽  
Spatial Segregation ◽  
Signaling Specificity ◽  
Physiological Processes ◽  
Intracellular Calcium Signaling ◽  
Specificity Effect ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We developed a two-dimensional model of transport-dependent intracellular calcium signaling in endothelial cells (ECs). Our purpose was to evaluate the effects of spatial colocalization of endothelial nitric oxide synthase (eNOS) and capacitative calcium entry (CCE) channels in caveolae on eNOS activation in response to ATP. Caveolae are specialized microdomains of the plasma membrane that contain a variety of signaling molecules to optimize their interactions and regulate their activity. In ECs, these molecules include CCE channels and eNOS. To achieve a quantitative understanding of the mechanisms of microdomain calcium signaling and the preferential sensitivity of eNOS to calcium entering the cell through CCE channels, we constructed a mathematical model incorporating the cell morphology and cellular physiological processes. The model predicts that the spatial segregation of calcium channels in ECs can create transport-dependent sharp gradients in calcium concentration within the cell. The calcium concentration gradient is affected by channel density and cell geometry. This transport-dependent calcium signaling specificity effect is enhanced in ECs by increasing the spatial segregation of the caveolar signaling domains. Our simulation significantly advances the understanding of how Ca2+, despite its many potential actions, can mediate selective activation of signaling pathways. We show that diffusion-limited calcium transport allows functional compartmentalization of signaling pathways based on the spatial arrangements of Ca2+ sources and targets.

scholarly journals Epithelial Na+ channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice

2018 ◽  
Vol 314 (5) ◽  
pp. H1022-H1032 ◽  
Author(s):  
Zoe Ashley ◽  
Sama Mugloo ◽  
Fiona J. McDonald ◽  
Martin Fronius
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Nitric Oxide Synthase ◽  
Signaling Pathways ◽  
Endothelial Nitric Oxide Synthase ◽  
Mesenteric Arteries ◽  
Intraluminal Pressure ◽  
Resistance Arteries ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

A potential “new player” in arteries for mediating shear stress responses is the epithelial Na+ channel (ENaC). The contribution of ENaC as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance), is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (third-order mesenteric) arteries isolated from C57Bl/6J mice. Vessel characteristics were determined at baseline (60 mmHg, no flow) and in response to increased intraluminal pressure and shear stress using a pressure myograph. These protocols were performed in the absence and presence of the ENaC inhibitor amiloride (10 µM) and after inhibition of endothelial nitric oxide synthase (eNOS) by Nω-nitro-l-arginine methyl ester (l-NAME; 100 µM). Under no-flow conditions, amiloride increased internal and external diameters of carotid (13 ± 2%, P < 0.05) but not mesenteric (0.5 ± 0.9%, P > 0.05) arteries. In response to increased intraluminal pressure, amiloride had no effect on the internal diameter of either type of artery. However, amiloride affected the stress-strain curves of mesenteric arteries. With increased shear stress, ENaC-dependent effects were observed in both arteries. In carotid arteries, amiloride augmented flow-mediated dilation (9.2 ± 5.3%) compared with control (no amiloride, 6.2 ± 3.3%, P < 0.05). In mesenteric arteries, amiloride induced a flow-mediated constriction (−11.5 ± 6.6%) compared with control (−2.2 ± 4.5%, P < 0.05). l-NAME mimicked the effect of ENaC inhibition and prevented further amiloride effects in both types of arteries. These observations indicate that ENaC contributes to shear sensing in conduit and resistance arteries. ENaC-mediated effects were associated with NO production but may involve different (artery-dependent) downstream signaling pathways. NEW & NOTEWORTHY The epithelial Na+ channel (ENaC) contributes to shear sensing in conduit and resistance arteries. In conduit arteries ENaC has a role as a vasoconstrictor, whereas in resistance arteries ENaC contributes to vasodilation. Interaction of ENaC with endothelial nitric oxide synthase/nitric oxide signaling to mediate the effects is supported; however, cross talk with other shear stress-dependent signaling pathways cannot be excluded. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/different-roles-of-enac-in-carotid-and-mesenteric-arteries/ .

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