Verma2016 - Ca(2+) Signal Propagation Along Hepatocyte Cords
This model is described in the article:
Abstract:
The purpose of this study is to model the dynamics of lobular Ca(2+) wave propagation induced by an extracellular stimulus, and to analyze the effect of spatially systematic variations in cell-intrinsic signaling parameters on sinusoidal Ca(2+) response.We developed a computational model of lobular scale Ca(2+) signaling that accounts for receptor- mediated initiation of cell-intrinsic Ca(2+) signal in hepatocytes and its propagation to neighboring hepatocytes through gap junction-mediated molecular exchange.Analysis of the simulations showed that a pericentral-to-periportal spatial gradient in hormone sensitivity and/or rates of IP3 synthesis underlies the Ca(2+) wave propagation. We simulated specific cases corresponding to localized disruptions in the graded pattern of these parameters along a hepatic sinusoid. Simulations incorporating locally altered parameters exhibited Ca(2+) waves that do not propagate throughout the hepatic plate. Increased gap junction coupling restored normal Ca(2+) wave propagation when hepatocytes with low Ca(2+) signaling ability were localized in the midlobular or the pericentral region.Multiple spatial patterns in intracellular signaling parameters can lead to Ca(2+) wave propagation that is consistent with the experimentally observed spatial patterns of Ca(2+) dynamics. Based on simulations and analysis, we predict that increased gap junction-mediated intercellular coupling can induce robust Ca(2+) signals in otherwise poorly responsive hepatocytes, at least partly restoring the sinusoidally oriented Ca (2+) waves.Our bottom-up model of agonist-evoked spatial Ca(2+) patterns can be integrated with detailed descriptions of liver histology to study Ca(2+) regulation at the tissue level.
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Computational Modeling of Spatiotemporal Ca(2+) Signal Propagation Along Hepatocyte Cords.
- Verma A, Makadia H, Hoek JB, Ogunnaike BA, Vadigepalli R.
- IEEE Trans Biomed Eng 2016 Oct; 63(10): 2047-2055 , 10/ 2016 , Volume 63 , Issue 10 , pages: 2047-2055 , PubMed ID: 27076052
- Aalap Verma, Department of Biomedical Engineering, University of Delaware, Newark, DE and the Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA;
- The purpose of this study is to model the dynamics of lobular Ca(2+) wave propagation induced by an extracellular stimulus, and to analyze the effect of spatially systematic variations in cell-intrinsic signaling parameters on sinusoidal Ca(2+) response.We developed a computational model of lobular scale Ca(2+) signaling that accounts for receptor- mediated initiation of cell-intrinsic Ca(2+) signal in hepatocytes and its propagation to neighboring hepatocytes through gap junction-mediated molecular exchange.Analysis of the simulations showed that a pericentral-to-periportal spatial gradient in hormone sensitivity and/or rates of IP3 synthesis underlies the Ca(2+) wave propagation. We simulated specific cases corresponding to localized disruptions in the graded pattern of these parameters along a hepatic sinusoid. Simulations incorporating locally altered parameters exhibited Ca(2+) waves that do not propagate throughout the hepatic plate. Increased gap junction coupling restored normal Ca(2+) wave propagation when hepatocytes with low Ca(2+) signaling ability were localized in the midlobular or the pericentral region.Multiple spatial patterns in intracellular signaling parameters can lead to Ca(2+) wave propagation that is consistent with the experimentally observed spatial patterns of Ca(2+) dynamics. Based on simulations and analysis, we predict that increased gap junction-mediated intercellular coupling can induce robust Ca(2+) signals in otherwise poorly responsive hepatocytes, at least partly restoring the sinusoidally oriented Ca (2+) waves.Our bottom-up model of agonist-evoked spatial Ca(2+) patterns can be integrated with detailed descriptions of liver histology to study Ca(2+) regulation at the tissue level.
Submitter of this revision: Mohammad Umer Sharif Shohan
Modellers: Aalap Verma, Mohammad Umer Sharif Shohan
Metadata information
isDescribedBy (3 statements)
isInstanceOf (4 statements)
Gene Ontology calcium-mediated signaling
BioModels Database MODEL1603110003
Brenda Tissue Ontology hepatocyte
hasProperty (2 statements)
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| Verma2016.xml | SBML L2V4 Ca(2+) Signal Propagation Along Hepatocyte Cords | 338.35 KB | Preview | Download |
Additional files |
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| MODEL1603110003.png | Auto-generated Reaction graph (PNG) | 939.22 KB | Preview | Download |
| MODEL1603110003.sci | Auto-generated Scilab file | 67.00 Bytes | Preview | Download |
| MODEL1603110003.svg | Auto-generated Reaction graph (SVG) | 248.16 KB | Preview | Download |
| MODEL1603110003.vcml | Auto-generated VCML file | 897.00 Bytes | Preview | Download |
| MODEL1603110003_url.xml | old xml file | 354.61 KB | Preview | Download |
| MODEL1603110003_urn.xml | Auto-generated SBML file with URNs | 354.60 KB | Preview | Download |
| Verma2016.cps | COPASI version 4.24 (Build 197) Ca(2+) Signal Propagation Along Hepatocyte Cords | 674.81 KB | Preview | Download |
| Verma2016.sedml | SEDML L1V2 Ca(2+) Signal Propagation Along Hepatocyte Cords | 1.01 KB | Preview | Download |
- Model originally submitted by : Aalap Verma
- Submitted: Mar 11, 2016 10:30:16 PM
- Last Modified: Oct 15, 2019 1:36:13 PM
Revisions
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Version: 5
- Submitted on: Oct 15, 2019 1:36:13 PM
- Submitted by: Mohammad Umer Sharif Shohan
- With comment: Automatically added model identifier BIOMD0000000834
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Version: 2
- Submitted on: Jun 12, 2017 4:15:23 PM
- Submitted by: Aalap Verma
- With comment: Current version of Verma2016 - Ca(2+) Signal Propagation Along Hepatocyte Cords
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Version: 1
- Submitted on: Mar 11, 2016 10:30:16 PM
- Submitted by: Aalap Verma
- With comment: Original import of Verma_Ca_Waves_Hepatocyte_Cords_2016
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revisions as only public revisions are displayed here. Any private revisions
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| g 7 | 0.25 item |
| IP3 7 | 0.1 item |
| g 8 | 0.25 item |
| IP3 10 | 0.1 item |
| r 11 | 0.5 item |
| g 12 | 0.25 item |
| g 13 | 0.25 item |
| r 13 | 0.5 item |
| IP3 6 | 0.1 item |
| CaI 7 | 0.2 item |
| Reactions | Rate | Parameters |
|---|---|---|
| g_7 => ; CaI_7 | cytosol7*F | F = 0.01 |
| IP3_7 => | cytosol7*0.5*D*IP3_7 | D = 1.6 |
| g_8 => ; CaI_8 | cytosol8*F | F = 0.01 |
| IP3_10 => IP3_9 | G*(IP3_10+(-IP3_9))*cytosol10 | G = 0.9 |
| => r_11 | cytosol11*k_r11 | k_r11 = 1.428571 |
| g_12 => ; CaI_12 | cytosol12*F | F = 0.01 |
| => g_13; CaI_13 | cytosol13*E*CaI_13^4*(1+(-g_13)) | E = 1.0 |
| => r_13 | cytosol13*k_r13 | k_r13 = 1.214286 |
| IP3_6 => IP3_5 | G*(IP3_6+(-IP3_5))*cytosol6 | G = 0.9 |
| CaT_7 => CaI_7; g_7, IP3_7 | (1+(-g_7))*(A*(0.5*IP3_7)^4*1/(k1+0.5*IP3_7)^4+L)*(CaT_7+(-CaI_7))*store7 | L = 1.5E-4; A = 0.2; k1 = 0.5 |
(added: 15 Oct 2019, 13:35:36, updated: 15 Oct 2019, 13:35:36)