126650
is: SBO:0000196
constant: true
units: 838742
value: 1.0
type: Parameter

838802
unit: 838850
unit: 838838
unit: 838826
unit: 838814
name: L per volt per sec per m^2
type: SBMLUnitsDef

839508
stoichiometry: 1.0
species: meta bl
type: SpeciesReference

839179
stoichiometry: 1.0
species: meta bi
type: SpeciesReference

838718
exponent: 1.0
scale: -3
multipler: 1.0
kind: MOLE
type: SBMLUnit

126664
is: SBO:0000345
constant: true
units: second
value: 60.0
type: Parameter

838730
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

126657
is: SBO:0000002
constant: true
units: 838706
value: 25.0
type: Parameter

839203
stoichiometry: 1.0
species: meta cl
type: SpeciesReference

839056
exponent: 1.0
scale: 0
multipler: 1.0
kind: COULOMB
type: SBMLUnit

126644
is: SBO:0000196
constant: true
units: 838706
value: 15.0
type: Parameter

839104
stoichiometry: 2.0
species: meta bb
type: SpeciesReference

ORG:
  orgname: EMBL-EBI
n:
  given: Lukas
  family: Endler

126637
is: SBO:0000009
constant: true
units: 838706
value: 10.0
type: Parameter

126580
type: Reaction
product: 839130
reactant: 839117
product: 839142
reactant: 839104
is: SBO:0000185
kinetic law: 839155
reversible: true
fast: false

126594
kinetic law: 839520
reactant: 839508
is: SBO:0000185
fast: false
reversible: true
type: Reaction

839117
stoichiometry: 1.0
species: meta nb
type: SpeciesReference

meta lumen
is: SBO:0000290
constant: true
size: 0.1
spatial dimensions: 3.0
name: lumen
type: Compartment

839277
stoichiometry: 1.0
species: meta cl
type: SpeciesReference

meta bb
in compartment: meta plasma
type: Species
has only substance units: false
is: CHEBI:17544
boundary condition: true
constant: true
initial concentration: 22.0
initial amount: NaN
name: HCO3-
is: SBO:0000327

838874
exponent: 1.0
scale: -3
multipler: 1.0
kind: MOLE
type: SBMLUnit

839313
stoichiometry: 1.0
species: meta ci
type: SpeciesReference

126677
constant: false
units: 838862
value: NaN
type: Parameter

838862
unit: 838899
unit: 838886
unit: 838874
name: mmol per sec per m^2
type: SBMLUnitsDef

839216
stoichiometry: 1.0
species: meta ci
type: SpeciesReference

126684
constant: false
units: 838947
value: NaN
type: Parameter

126670
constant: false
units: volt
value: NaN
type: Parameter

839532
persistant: true
initial value: true
type: Trigger

meta bi
initial amount: NaN
type: Species
has only substance units: false
boundary condition: false
is: SBO:0000327
in compartment: meta cell
constant: false
is: CHEBI:17544
name: HCO3-
initial concentration: 15.0

839460
stoichiometry: 1.0
species: meta bl
type: SpeciesReference

126581
kinetic law: 839191
product: 839179
reactant: 839167
is: SBO:0000185
fast: false
reversible: true
type: Reaction

838742
unit: 838790
unit: 838778
unit: 838766
unit: 838754
name: mmol per volt per sec per m^2
type: SBMLUnitsDef

838935
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

838996
unit: 839032
unit: 839020
unit: 839008
name: J per mol per K
type: SBMLUnitsDef

meta ni
constant: false
has only substance units: false
initial concentration: 14.0
in compartment: meta cell
initial amount: NaN
is: CHEBI:29101
name: Na+
type: Species
boundary condition: false
is: SBO:0000327

839142
stoichiometry: 1.0
species: meta ni
type: SpeciesReference

126652
is: SBO:0000568
constant: true
units: 839044
value: 96485.0
name: Faraday constant
type: Parameter

126681
constant: false
units: 838862
value: NaN
type: Parameter

838706
unit: 838730
unit: 838718
name: mM
type: SBMLUnitsDef

126679
constant: false
units: 838862
value: NaN
type: Parameter

126669
constant: false
units: volt
value: NaN
type: Parameter

839044
unit: 839068
unit: 839056
name: C per mol
type: SBMLUnitsDef

126659
is: SBO:0000009
constant: true
units: volt
value: -0.2
type: Parameter

126662
is: SBO:0000002
constant: true
units: dimensionless
value: 0.25
type: Parameter

126671
constant: false
units: volt
value: NaN
type: Parameter

838983
exponent: -2.0
scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

839265
stoichiometry: 1.0
species: meta bi
type: SpeciesReference

838886
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

839325
stoichiometry: 1.0
species: meta bi
type: SpeciesReference

126642
is: SBO:0000196
constant: true
units: dimensionless
value: 10.0
type: Parameter

126639
is: SBO:0000257
constant: true
units: 838742
value: 2.0
type: Parameter

839398
stoichiometry: 1.0
species: meta ni
type: SpeciesReference

126632
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constant: true
units: dimensionless
value: 0.2
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126649
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constant: true
units: volt
value: -0.085
type: Parameter

126592
kinetic law: 839472
product: 839460
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fast: false
reversible: true
type: Reaction

838790
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reversible: true
type: Reaction

126682
constant: false
units: 838862
value: NaN
type: Parameter

839337
stoichiometry: 1.0
species: meta cb
type: SpeciesReference

126651
is: SBO:0000567
constant: true
units: 838996
value: 8.31451
name: gas constant
type: Parameter

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scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

838838
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

126661
is: SBO:0000002
constant: true
units: 838862
value: 0.025
type: Parameter

126672
constant: false
units: 838742
value: NaN
type: Parameter

126593
kinetic law: 839496
product: 839484
is: SBO:0000185
fast: false
reversible: true
type: Reaction

839557
persistant: true
initial value: true
type: Trigger

126641
is: SBO:0000257
constant: true
units: 838742
value: 0.005
type: Parameter

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exponent: 2.0
scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

839130
stoichiometry: 2.0
species: meta bi
type: SpeciesReference

839410
stoichiometry: 1.0
species: meta nb
type: SpeciesReference

BIOMD0000000327
parameter: 126661
parameter: 126651
species: meta cb
curated: true
reaction: 126580
units def: 839044
parameter: 126677
species: meta ni
reaction: 126594
reaction: 126584
parameter: 126664
parameter: 126654
function def: 126630
species: meta bb
parameter: 126634
reaction: 126587
species: meta nb
rule: 126619
area units: area
parameter: 126640
name: Whitcomb2004_Bicarbonate_Pancreas
rule: 126610
occurs in: http://identifiers.org/taxonomy/9606
parameter: 126679
parameter: 126647
parameter: 126637
compartment: meta lumen
parameter: 126656
parameter: 126681
parameter: 126671
rule: 126614
rule: 126613
rule: 126623
time units: 759753
parameter: 126650
parameter: 126680
parameter: 126657
parameter: 126684
parameter: 126686
parameter: 126676
species: meta bl
reaction: 126593
event: 126606
units def: 838706
notes: A mathematical model of the pancreatic duct cell generating high bicarbonate concentrations in pancreatic juice David C Whitcomb, G Bard Ermentrout, Pancreas 2004 29:e30-40; PubMedID: 15257112 Abstract: OBJECTIVE: To develop a simple, physiologically based mathematical model of pancreatic duct cell secretion using experimentally derived parameters that generates pancreatic fluid bicarbonate concentrations of >140 mM after CFTR activation. METHODS: A new mathematical model was developed simulating a duct cell within a proximal pancreatic duct and included a sodium-2-bicarbonate cotransporter (NBC) and sodium-potassium pump (NaK pump) on a chloride-impermeable basolateral membrane, CFTR on the luminal membrane with 0.2 to 1 bicarbonate to chloride permeability ratio. Chloride-bicarbonate antiporters (Cl/HCO3 AP) were added or subtracted from the basolateral (APb) and luminal (APl) membranes. The model was integrated over time using XPPAUT. RESULTS: This model predicts robust, NaK pump-dependent bicarbonate secretion with opening of the CFTR, generates and maintains pancreatic fluid secretion with bicarbonate concentrations >140 mM, and returns to basal levels with CFTR closure. Limiting CFTR permeability to bicarbonate, as seen in some CFTR mutations, markedly inhibited pancreatic bicarbonate and fluid secretion. CONCLUSIONS: A simple CFTR-dependent duct cell model can explain active, high-volume, high-concentration bicarbonate secretion in pancreatic juice that reproduces the experimental findings. This model may also provide insight into why CFTR mutations that predominantly affect bicarbonate permeability predispose to pancreatic dysfunction in humans. This SBML version of the model was created directly from the XPPAUT code found in the appendix with the exception of the parameter vr , the ratio between the duct cell volume and the duct lumen, which is defined inversely to the main text in the XPPAUT code. vr was defined as the ratio of the duct cell volume to the …
units def: 838742
units def: 838682
reaction: 126592
volume units: 749163
reaction: 126586
species: meta cl
units def: 838802
compartment: meta cell
parameter: 126666
compartment: meta plasma
rule: 126620
parameter: 126646
parameter: 126636
rule: 126625
species: meta ci
occurs in: BTO:0002362
initial assignment: BIOMD0000000327#
type: SBMLModel
parameter: 126670
rule: 126615
is: MODEL1104180000
parameter: 126642
parameter: 126632
rule: 126624
units def: 838862
reaction: 126590
parameter: 126649
parameter: 126639
substance units: 838682
parameter: 126685
parameter: 126675
reaction: 126582
parameter: 126660
parameter: 126662
parameter: 126652

838754
exponent: 1.0
scale: -3
multipler: 1.0
kind: MOLE
type: SBMLUnit

839008
exponent: 1.0
scale: 0
multipler: 1.0
kind: JOULE
type: SBMLUnit

126606
event assignment: 839569
trigger: 839557
use values from trigger time: true
type: Event

838694
exponent: 1.0
scale: -3
multipler: 1.0
kind: MOLE
type: SBMLUnit

meta cb
is: SBO:0000327
in compartment: meta plasma
initial amount: NaN
is: CHEBI:17996
boundary condition: true
has only substance units: false
name: CL-
constant: true
type: Species
initial concentration: 130.0

838971
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

126654
is: SBO:0000002
constant: true
units: kelvin
value: 310.0
type: Parameter

126584
kinetic law: 839289
is: SBO:0000185
reactant: 839252
product: 839265
product: 839277
fast: false
reversible: true
reactant: 839240
type: Reaction

126647
is: SBO:0000196
constant: true
units: 838802
value: 7.0E-5
type: Parameter

838826
exponent: -1.0
scale: 0
multipler: 1.0
kind: VOLT
type: SBMLUnit

839252
stoichiometry: 1.0
species: meta ci
type: SpeciesReference

126660
is: SBO:0000009
constant: true
units: 838742
value: 0.4
type: Parameter

839484
stoichiometry: 1.0
species: meta cl
type: SpeciesReference

126640
is: SBO:0000257
constant: true
units: 838742
value: 0.25
type: Parameter

838899
exponent: -2.0
scale: 0
multipler: 1.0
kind: METRE
type: SBMLUnit

839032
exponent: -1.0
scale: 0
multipler: 1.0
kind: KELVIN
type: SBMLUnit

126680
constant: false
units: 838862
value: NaN
type: Parameter

126605
event assignment: 839545
trigger: 839532
use values from trigger time: true
type: Event

838766
exponent: -1.0
scale: 0
multipler: 1.0
kind: VOLT
type: SBMLUnit

838959
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

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initial amount: NaN
name: CL-
is: CHEBI:17996
is: SBO:0000327
in compartment: meta cell
has only substance units: false
boundary condition: false
initial concentration: 60.0
type: Species

126585
reactant: 839301
product: 839337
product: 839325
reversible: true
is: SBO:0000185
type: Reaction
reactant: 839313
kinetic law: 839349
fast: false

126674
constant: false
units: 838742
value: NaN
type: Parameter

126667
constant: false
units: volt
value: NaN
type: Parameter

126634
is: SBO:0000009
constant: true
units: dimensionless
value: 1.0
type: Parameter

meta plasma
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: plasma
type: Compartment

126666
is: SBO:0000196
constant: false
units: 838802
value: NaN
type: Parameter

839301
stoichiometry: 1.0
species: meta bb
type: SpeciesReference

838682
unit: 838694
name: mmol
type: SBMLUnitsDef

meta cl
in compartment: meta lumen
is: CHEBI:17996
name: CL-
is: SBO:0000327
initial amount: NaN
constant: false
type: Species
boundary condition: true
has only substance units: false
initial concentration: NaN

839374
stoichiometry: 1.0
species: meta nb
type: SpeciesReference

838911
unit: 838935
unit: 838923
name: m^2 per L
type: SBMLUnitsDef

839167
stoichiometry: 1.0
species: meta bl
type: SpeciesReference

126675
constant: false
units: 838742
value: NaN
type: Parameter

126586
kinetic law: 839386
product: 839374
reactant: 839362
is: SBO:0000185
fast: false
reversible: true
type: Reaction

126656
is: SBO:0000009
constant: true
units: 838742
value: 3.125
type: Parameter

126645
is: SBO:0000196
constant: true
units: 838947
value: 0.1
type: Parameter

meta nb
boundary condition: true
type: Species
initial amount: NaN
is: CHEBI:29101
in compartment: meta plasma
name: Na+
constant: true
is: SBO:0000327
initial concentration: 140.0
has only substance units: false

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scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

126635
is: SBO:0000009
constant: true
units: 838911
value: 50.0
type: Parameter

126685
constant: false
units: 838862
value: NaN
type: Parameter

839240
stoichiometry: 1.0
species: meta bl
type: SpeciesReference

meta bl
constant: false
has only substance units: false
initial concentration: 32.0
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name: HCO3-
is: SBO:0000327
type: Species
in compartment: meta lumen
initial amount: NaN
boundary condition: false

838778
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

838947
unit: 838983
unit: 838971
unit: 838959
name: L per sec per m^2
type: SBMLUnitsDef

meta cell
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: cell
type: Compartment

126665
is: SBO:0000345
constant: true
units: second
value: 360.0
type: Parameter

126655
is: SBO:0000196
constant: true
units: 838706
value: 160.0
type: Parameter

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exponent: -1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

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product: 839435
is: SBO:0000176
fast: false
reversible: true
type: Reaction

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stoichiometry: 1.0
species: meta bi
type: SpeciesReference

126587
kinetic law: 839423
product: 839410
reactant: 839398
is: SBO:0000185
fast: false
reversible: true
type: Reaction

126676
constant: false
units: volt
value: NaN
type: Parameter

839362
stoichiometry: 1.0
species: meta ni
type: SpeciesReference

126646
is: SBO:0000196
constant: true
units: 838802
value: 1.0
type: Parameter

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exponent: -1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

126636
is: SBO:0000009
constant: true
units: 838706
value: 1.0
type: Parameter

126686
constant: false
units: 838862
value: NaN
type: Parameter

ORG:
  orgname: University of Manchester
n:
  given: Kieran
  family: Smallbone

W3 CDTF: Thu Apr 14 01:00:00 BST 2011

W3 CDTF: Tue May 15 22:55:21 BST 2012