BIOMD0000000327
type: SBMLModel
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
species: meta ci
occurs in: BTO:0002362
initial assignment: BIOMD0000000327#
parameter: 126670
rule: 126625
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

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

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

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

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

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

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

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

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

839020
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: MOLE

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

meta cb
type: Species
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
initial concentration: 130.0

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

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

839130
type: SpeciesReference
stoichiometry: 2.0
species: meta bi

meta bi
type: Species
initial amount: NaN
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

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

839117
type: SpeciesReference
stoichiometry: 1.0
species: meta nb

meta nb
type: Species
boundary condition: true
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

839142
type: SpeciesReference
stoichiometry: 1.0
species: meta ni

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

839104
type: SpeciesReference
stoichiometry: 2.0
species: meta bb

meta bb
type: Species
in compartment: meta plasma
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

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

839068
type: SBMLUnit
exponent: -1.0
scale: 0
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kind: MOLE

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

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

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

839508
type: SpeciesReference
stoichiometry: 1.0
species: meta bl

meta bl
type: Species
constant: false
has only substance units: false
initial concentration: 32.0
is: CHEBI:17544
name: HCO3-
is: SBO:0000327
in compartment: meta lumen
initial amount: NaN
boundary condition: false

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

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

839252
type: SpeciesReference
stoichiometry: 1.0
species: meta ci

meta ci
type: Species
constant: false
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

839265
type: SpeciesReference
stoichiometry: 1.0
species: meta bi

839277
type: SpeciesReference
stoichiometry: 1.0
species: meta cl

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

839240
type: SpeciesReference
stoichiometry: 1.0
species: meta bl

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

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

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

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

839410
type: SpeciesReference
stoichiometry: 1.0
species: meta nb

839398
type: SpeciesReference
stoichiometry: 1.0
species: meta ni

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

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

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multipler: 1.0
kind: METRE

838778
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kind: SECOND

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

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

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

126647
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constant: true
units: 838802
value: 7.0E-5

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

838850
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scale: 0
multipler: 1.0
kind: METRE

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

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

838814
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

839484
type: SpeciesReference
stoichiometry: 1.0
species: meta cl

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

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

839557
type: Trigger
persistant: true
initial value: true

838682
type: SBMLUnitsDef
unit: 838694
name: mmol

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

126592
type: Reaction
kinetic law: 839472
product: 839460
is: SBO:0000185
fast: false
reversible: true

839460
type: SpeciesReference
stoichiometry: 1.0
species: meta bl

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

839374
type: SpeciesReference
stoichiometry: 1.0
species: meta nb

839362
type: SpeciesReference
stoichiometry: 1.0
species: meta ni

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

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

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

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

126632
type: Parameter
is: SBO:0000009
constant: true
units: dimensionless
value: 0.2

126590
type: Reaction
kinetic law: 839447
product: 839435
is: SBO:0000176
fast: false
reversible: true

839435
type: SpeciesReference
stoichiometry: 1.0
species: meta bi

126649
type: Parameter
is: SBO:0000196
constant: true
units: volt
value: -0.085

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

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

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

126582
type: Reaction
kinetic law: 839228
product: 839216
reactant: 839203
is: SBO:0000185
fast: false
reversible: true

839216
type: SpeciesReference
stoichiometry: 1.0
species: meta ci

839203
type: SpeciesReference
stoichiometry: 1.0
species: meta cl

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

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

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

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

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

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

839179
type: SpeciesReference
stoichiometry: 1.0
species: meta bi

839167
type: SpeciesReference
stoichiometry: 1.0
species: meta bl

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

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

838923
type: SBMLUnit
exponent: 2.0
scale: 0
multipler: 1.0
kind: METRE

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

839532
type: Trigger
persistant: true
initial value: true

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

839301
type: SpeciesReference
stoichiometry: 1.0
species: meta bb

839337
type: SpeciesReference
stoichiometry: 1.0
species: meta cb

839325
type: SpeciesReference
stoichiometry: 1.0
species: meta bi

839313
type: SpeciesReference
stoichiometry: 1.0
species: meta ci

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

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

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

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

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

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

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

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

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

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

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

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

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

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