Purvis2008 - A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y1 activation
Model Identifier
MODEL1805150001
Short description
Mathematical model
Format
SBML
(L2V4)
Related Publication
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A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y1 activation.
- Purvis JE, Chatterjee MS, Brass LF, Diamond SL
- Blood , 11/ 2008 , Volume 112 , Issue 10 , pages: 4069-4079 , PubMed ID: 18596227
- Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, USA.
- To quantify how various molecular mechanisms are integrated to maintain platelet homeostasis and allow responsiveness to adenosine diphosphate (ADP), we developed a computational model of the human platelet. Existing kinetic information for 77 reactions, 132 fixed kinetic rate constants, and 70 species was combined with electrochemical calculations, measurements of platelet ultrastructure, novel experimental results, and published single-cell data. The model accurately predicted: (1) steady-state resting concentrations for intracellular calcium, inositol 1,4,5-trisphosphate, diacylglycerol, phosphatidic acid, phosphatidylinositol, phosphatidylinositol phosphate, and phosphatidylinositol 4,5-bisphosphate; (2) transient increases in intracellular calcium, inositol 1,4,5-trisphosphate, and G(q)-GTP in response to ADP; and (3) the volume of the platelet dense tubular system. A more stringent test of the model involved stochastic simulation of individual platelets, which display an asynchronous calcium spiking behavior in response to ADP. Simulations accurately reproduced the broad frequency distribution of measured spiking events and demonstrated that asynchronous spiking was a consequence of stochastic fluctuations resulting from the small volume of the platelet. The model also provided insights into possible mechanisms of negative-feedback signaling, the relative potency of platelet agonists, and cell-to-cell variation across platelet populations. This integrative approach to platelet biology offers a novel and complementary strategy to traditional reductionist methods.
Contributors
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts
Metadata information
isDescribedBy (1 statement)
isVersionOf (3 statements)
hasPart (1 statement)
isVersionOf (3 statements)
Gene Ontology
regulation of calcium-mediated signaling
Gene Ontology regulation of platelet formation
Gene Ontology homeostatic process
Gene Ontology regulation of platelet formation
Gene Ontology homeostatic process
hasPart (1 statement)
Curation status
Non-curated
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
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Model files |
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| Purvis2008.xml | SBML L2V4 representation of Purvis2008 - A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y1 activation | 278.45 KB | Preview | Download |
Additional files |
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| Purvis2008.cps | uncurated and slightly annotated model COPASI file. Missing parameters (L3, L1) for reaction 8? Reaction 12 and 13 not dependent on reactants (changed so that it is dependent)? Reaction 15 and 17 has the wrong reactant (PLC-B* vs PI)? Modifiers added to reactions 20-29. Reactions 47-50 - added species (GDP/GTP) so that reaction is consistent with kinetic laws? | 459.66 KB | Preview | Download |
- Model originally submitted by : Matthew Roberts
- Submitted: May 15, 2018 5:20:53 PM
- Last Modified: May 15, 2018 5:20:53 PM
Revisions
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Version: 2
- Submitted on: May 15, 2018 5:20:53 PM
- Submitted by: Matthew Roberts
- With comment: Edited model metadata online.