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BIOMD0000000400 - Cooling2007_IP3transients_CardiacMyocyte

 

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Reference Publication
Publication ID: 17693463
Cooling M, Hunter P, Crampin EJ.
Modeling hypertrophic IP3 transients in the cardiac myocyte.
Biophys. J. 2007 Nov; 93(10): 3421-3433
Auckland Bioengineering Institute, Department of Engineering Science, University of Auckland, New Zealand. m.cooling@auckland.ac.nz  [more]
Model
Original Model: CellML logo
Submitter: Vijayalakshmi Chelliah
Submission ID: MODEL0913194523
Submission Date: 28 Apr 2009 11:55:20 UTC
Last Modification Date: 06 Apr 2014 23:21:28 UTC
Creation Date: 28 Apr 2009 11:55:20 UTC
Encoders:  Mike Cooling
set #1
bqbiol:isVersionOf Gene Ontology heart process
Gene Ontology inositol phosphate-mediated signaling
Gene Ontology cardiac muscle hypertrophy
set #2
bqbiol:isVersionOf FMA FMA:83108
bqbiol:hasTaxon Taxonomy Mus musculus
set #3
bqmodel:is Mathematical Modelling Ontology MAMO_0000046
Notes

This a model from the article:
Modeling hypertrophic IP3 transients in the cardiac myocyte.
Cooling M, Hunter P, Crampin EJ. Biophys J2007 Nov 15;93(10):3421-33 17693463,
Abstract:
Cardiac hypertrophy is a known risk factor for heart disease, and at the cellular level is caused by a complex interaction of signal transduction pathways. The IP3-calcineurin pathway plays an important role in stimulating the transcription factor NFAT which binds to DNA cooperatively with other hypertrophic transcription factors. Using available kinetic data, we construct a mathematical model of the IP3 signal production system after stimulation by a hypertrophic alpha-adrenergic agonist (endothelin-1) in the mouse atrial cardiac myocyte. We use a global sensitivity analysis to identify key controlling parameters with respect to the resultant IP3 transient, including the phosphorylation of cell-membrane receptors, the ligand strength and binding kinetics to precoupled (with G(alpha)GDP) receptor, and the kinetics associated with precoupling the receptors. We show that the kinetics associated with the receptor system contribute to the behavior of the system to a great extent, with precoupled receptors driving the response to extracellular ligand. Finally, by reparameterizing for a second hypertrophic alpha-adrenergic agonist, angiotensin-II, we show that differences in key receptor kinetic and membrane density parameters are sufficient to explain different observed IP3 transients in essentially the same pathway.

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: Cooling M, Hunter P, Crampin EJ. (2007) - version02
The original CellML model was created by:
Cooling, Mike,
m.cooling@aukland.ac.nz
The University of Auckland
The Bioengineering Institute

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 17693463 Submission Date: 28 Apr 2009 11:55:20 UTC Last Modification Date: 06 Apr 2014 23:21:28 UTC Creation Date: 28 Apr 2009 11:55:20 UTC
Mathematical expressions
Rules
Rate Rule (variable: P) Rate Rule (variable: Pg) Rate Rule (variable: Pc) Rate Rule (variable: Pcg)
Rate Rule (variable: IP3) Rate Rule (variable: Gd) Rate Rule (variable: Gt) Rate Rule (variable: Ca)
Rate Rule (variable: R) Rate Rule (variable: Rl) Rate Rule (variable: Rg) Rate Rule (variable: Rlgp)
Rate Rule (variable: Rlg) Assignment Rule (variable: Cc) Assignment Rule (variable: Cp) Assignment Rule (variable: Cpc)
Assignment Rule (variable: J13) Assignment Rule (variable: J12) Assignment Rule (variable: kr11) Assignment Rule (variable: J11)
Assignment Rule (variable: J10) Assignment Rule (variable: J8) Assignment Rule (variable: J9) Assignment Rule (variable: J16)
Assignment Rule (variable: J14) Assignment Rule (variable: J15) Assignment Rule (variable: J7) Assignment Rule (variable: L)
Assignment Rule (variable: kr1) Assignment Rule (variable: J1) Assignment Rule (variable: kr2) Assignment Rule (variable: J2)
Assignment Rule (variable: J3) Assignment Rule (variable: kr4) Assignment Rule (variable: J4) Assignment Rule (variable: J5)
Assignment Rule (variable: J6)      
Physical entities
Compartments Species
Compartment Gd Gt R
Rl Rg Rlg
Rlgp IP3 Pc
Pcg P Pg
Ca    
Global parameters
L Ls ts PIP2
J1 kf1 kr1 Kd1
J2 kf2 kr2 Kd2
J3 kf3 kr3 J4
kf4 kr4 Kd4 J5
kf5 J6 kf6 J7
kf7 J8 kf8 kr8
J9 kf9 kr9 J10
kf10 kr10 J11 kf11
kr11 Kd11 J12 kf12
J13 kf13 J14 kf14
Km14 J15 kf15 Km15
J16 kf16 Cpc Cc
Cp Vc Rpc  
Reactions (0)
Rules (37)
 
 Rate Rule (name: P) d [ P] / d t= J13-(J9+J8)
 
 Rate Rule (name: Pg) d [ Pg] / d t= J9-(J11+J13)
 
 Rate Rule (name: Pc) d [ Pc] / d t= J8+J12-J10
 
 Rate Rule (name: Pcg) d [ Pcg] / d t= J10+J11-J12
 
 Rate Rule (name: IP3) d [ IP3] / d t= Cpc*(J14+J15)-J16
 
 Rate Rule (name: Gd) d [ Gd] / d t= J7+J13+J12-(J2+J3)
 
 Rate Rule (name: Gt) d [ Gt] / d t= J6-(J7+J9+J10)
 
 Rate Rule (name: Ca) d [ Ca] / d t= Cpc*(-1)*(J8+J11)
 
 Rate Rule (name: R) d [ R] / d t= (-1)*(J1+J2)
 
 Rate Rule (name: Rl) d [ Rl] / d t= J1+J6-J3
 
 Rate Rule (name: Rg) d [ Rg] / d t= J2-J4
 
 Rate Rule (name: Rlgp) d [ Rlgp] / d t= J5
 
 Rate Rule (name: Rlg) d [ Rlg] / d t= J3-J5+J4-J6
 
 Assignment Rule (name: Cc) Cc = 1/(Vc*602.2)
 
 Assignment Rule (name: Cp) Cp = 1/(Vc*Rpc)
 
 Assignment Rule (name: Cpc) Cpc = Cc/Cp
 
 Assignment Rule (name: J13) J13 = kf13*Pg
 
 Assignment Rule (name: J12) J12 = kf12*Pcg
 
 Assignment Rule (name: kr11) kr11 = kf11*Kd11
 
 Assignment Rule (name: J11) J11 = kf11*Pg*Ca-kr11*Pcg
 
 Assignment Rule (name: J10) J10 = kf10*Pc*Gt-kr10*Pcg
 
 Assignment Rule (name: J8) J8 = kf8*P*Ca-kr8*Pc
 
 Assignment Rule (name: J9) J9 = kf9*P*Gt-kr9*Pg
 
 Assignment Rule (name: J16) J16 = kf16*IP3
 
 Assignment Rule (name: J14) J14 = kf14*Pc*PIP2/(Km14/Cpc+PIP2)
 
 Assignment Rule (name: J15) J15 = kf15*Pcg*PIP2/(Km15/Cpc+PIP2)
 
 Assignment Rule (name: J7) J7 = kf7*Gt
 
 Assignment Rule (name: L) L = piecewise(Ls/(1+exp((-80)*(time-ts-0.05))), (time < ts+0.15) && (time >= ts), Ls, time >= ts+0.15, 0)
 
 Assignment Rule (name: kr1) kr1 = kf1*Kd1
 
 Assignment Rule (name: J1) J1 = kf1*R*L-kr1*Rl
 
 Assignment Rule (name: kr2) kr2 = kf2*Kd2
 
 Assignment Rule (name: J2) J2 = kf2*R*Gd-kr2*Rg
 
 Assignment Rule (name: J3) J3 = kf3*Rl*Gd-kr3*Rlg
 
 Assignment Rule (name: kr4) kr4 = kf4*Kd4
 
 Assignment Rule (name: J4) J4 = kf4*L*Rg-kr4*Rlg
 
 Assignment Rule (name: J5) J5 = kf5*Rlg
 
 Assignment Rule (name: J6) J6 = kf6*Rlg
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 Gd
Compartment: Compartment
Initial concentration: 10000.0
 
 Gt
Compartment: Compartment
Initial concentration: 0.0
 
 R
Compartment: Compartment
Initial concentration: 13.9
 
 Rl
Compartment: Compartment
Initial concentration: 0.0
 
 Rg
Compartment: Compartment
Initial concentration: 5.06
 
 Rlg
Compartment: Compartment
Initial concentration: 0.0
 
 Rlgp
Compartment: Compartment
Initial concentration: 0.0
 
 IP3
Compartment: Compartment
Initial concentration: 0.015
 
 Pc
Compartment: Compartment
Initial concentration: 9.09
 
 Pcg
Compartment: Compartment
Initial concentration: 0.0
 
 P
Compartment: Compartment
Initial concentration: 90.9
 
 Pg
Compartment: Compartment
Initial concentration: 0.0
 
 Ca
Compartment: Compartment
Initial concentration: 0.1
 
Global Parameters (55)
 
   L
Value: NaN
 
 Ls
Value: 0.1
Constant
 
 ts
Value: 30.0
Constant
 
 PIP2
Value: 4000.0
Constant
 
   J1
Value: NaN
 
 kf1
Value: 3.0E-4
Constant
 
  kr1
Value: NaN
 
 Kd1
Value: 3.0E-5
Constant
 
   J2
Value: NaN
 
 kf2
Value: 2.75E-4
Constant
 
  kr2
Value: NaN
 
 Kd2
Value: 27500.0
Constant
 
   J3
Value: NaN
 
 kf3
Value: 1.0
Constant
 
 kr3
Value: 0.0010
Constant
 
   J4
Value: NaN
 
 kf4
Value: 0.3
Constant
 
  kr4
Value: NaN
 
 Kd4
Value: 3.0E-5
Constant
 
   J5
Value: NaN
 
 kf5
Value: 4.0E-4
Constant
 
   J6
Value: NaN
 
 kf6
Value: 1.0
Constant
 
   J7
Value: NaN
 
 kf7
Value: 0.15
Constant
 
   J8
Value: NaN
 
 kf8
Value: 0.0167
Constant
 
 kr8
Value: 0.0167
Constant
 
   J9
Value: NaN
 
 kf9
Value: 0.0042
Constant
 
 kr9
Value: 1.0
Constant
 
   J10
Value: NaN
 
 kf10
Value: 0.042
Constant
 
 kr10
Value: 1.0
Constant
 
   J11
Value: NaN
 
 kf11
Value: 0.0334
Constant
 
  kr11
Value: NaN
 
 Kd11
Value: 0.1
Constant
 
   J12
Value: NaN
 
 kf12
Value: 6.0
Constant
 
   J13
Value: NaN
 
 kf13
Value: 6.0
Constant
 
   J14
Value: NaN
 
 kf14
Value: 0.444
Constant
 
 Km14
Value: 19.8
Constant
 
   J15
Value: NaN
 
 kf15
Value: 3.8
Constant
 
 Km15
Value: 5.0
Constant
 
   J16
Value: NaN
 
 kf16
Value: 1.25
Constant
 
   Cpc
Value: NaN
 
   Cc
Value: NaN
 
   Cp
Value: NaN
 
 Vc
Value: 2550.0
Constant
 
 Rpc
Value: 4.61
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000400

Curator's comment: (updated: 17 Nov 2011 12:03:37 GMT)

Figure 3 of the reference publication has been reproduced here. The model was simulated using Copasi v4.7 (Build 34).

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