Journal article
Transport-dependent calcium signaling in spatially segregated cellular caveolar domains
American Journal of Physiology: Cell Physiology, v 294(3), pp C856-866
Mar 2008
PMID: 18160488
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Transport-dependent calcium signaling in spatially segregated cellular caveolar domains
- Creators
- Dihui Hong - School of Biomedical Engineering, Science, and Health Systems, Drexel Univ., Philadelphia, PA 19104, USADov JaronDonald G BuerkKenneth A Barbee
- Publication Details
- American Journal of Physiology: Cell Physiology, v 294(3), pp C856-866
- Publisher
- American Physiological Society (APS); United States
- Grant note
- HL-068164 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; [Retired Faculty]
- Web of Science ID
- WOS:000253992300019
- Scopus ID
- 2-s2.0-41549120593
- Other Identifier
- 991014878209404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Physiology