Verma2016 - Ca(2+) Signal Propagation Along Hepatocyte Cords

  public model
Model Identifier
BIOMD0000000834
Short description
Verma2016 - Ca(2+) Signal Propagation Along Hepatocyte Cords

This model is described in the article:

Verma A, Makadia H, Hoek JB, Ogunnaike BA, Vadigepalli R.
IEEE Trans Biomed Eng 2016 Oct; 63(10): 2047-2055

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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • 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.
Contributors
Submitter of the first revision: Aalap Verma
Submitter of this revision: Mohammad Umer Sharif Shohan
Modellers: Aalap Verma, Mohammad Umer Sharif Shohan

Metadata information

is (2 statements)
BioModels Database MODEL1603110003
BioModels Database BIOMD0000000834

isDescribedBy (3 statements)
PubMed 27076052
Taxonomy Homo sapiens
Brenda Tissue Ontology hepatocyte

isInstanceOf (4 statements)
Taxonomy Homo sapiens
Gene Ontology calcium-mediated signaling
BioModels Database MODEL1603110003
Brenda Tissue Ontology hepatocyte

hasProperty (2 statements)
Gene Ontology calcium-mediated signaling
BioModels Database MODEL1603110003


Curation status
Curated

Connected external resources

Name Description Size Actions

Model files

Verma2016.xml SBML L2V4 Ca(2+) Signal Propagation Along Hepatocyte Cords 338.35 KB Preview | Download

Additional files

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
  • Version: 5 public model Download this version
    • Submitted on: Oct 15, 2019 1:36:13 PM
    • Submitted by: Mohammad Umer Sharif Shohan
    • With comment: Automatically added model identifier BIOMD0000000834
  • Version: 2 public model Download this version
    • 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
  • Version: 1 public model Download this version
    • Submitted on: Mar 11, 2016 10:30:16 PM
    • Submitted by: Aalap Verma
    • With comment: Original import of Verma_Ca_Waves_Hepatocyte_Cords_2016

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
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
CaT 7 500.0 item
IP3 8 0.1 item
CaI 12 0.2 item
IP3 2 0.1 item
CaI 5 0.2 item
Reactions
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
CaI_7 => CaT_7 B*CaI_7^2*1/(k2^2+CaI_7^2)*cytosol7 B = 0.082; k2 = 0.15
IP3_8 => IP3_7 G*(IP3_8+(-IP3_7))*cytosol8 G = 0.9
CaI_12 => CaT_12 B*CaI_12^2*1/(k2^2+CaI_12^2)*cytosol12 B = 0.082; k2 = 0.15
IP3_1 => IP3_2 G*(IP3_1+(-IP3_2))*cytosol1 G = 0.9
CaT_5 => CaI_5; g_5, IP3_5 (1+(-g_5))*(A*(0.5*IP3_5)^4*1/(k1+0.5*IP3_5)^4+L)*(CaT_5+(-CaI_5))*store5 L = 1.5E-4; A = 0.2; k1 = 0.5
Curator's comment:
(added: 15 Oct 2019, 13:35:36, updated: 15 Oct 2019, 13:35:36)
Model is encoded in COPASI 4.24 (Build197) and plots are generated using R ggplot package. Model simulation time is 700 seconds. Figure 2 of the paper has been reproduced. Although the figure is similar in pattern but not exact. For the model the value was corrected for Parameter H(1e-4) and KH (1)was changed to the one provided in the xml file.