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BIOMD0000000636 - Nair2015 - Interaction between neuromodulators via GPCRs - Effect on cAMP/PKA signaling (D2 Neuron)

 

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Reference Publication
Publication ID: 26468202
Nair AG, Gutierrez-Arenas O, Eriksson O, Vincent P, Hellgren Kotaleski J.
Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons.
J. Neurosci. 2015 Oct; 35(41): 14017-14030
Science for Life Laboratory, School of Computer Science and Communication, KTH Royal Institute of Technology, 11428 Stockholm, Sweden, Manipal University, 576104 Manipal, India.  [more]
Model
Original Model: BIOMD0000000636.origin
Submitter: Anu G Nair
Submission ID: MODEL1502200001
Submission Date: 20 Feb 2015 11:19:40 UTC
Last Modification Date: 16 May 2017 13:20:10 UTC
Creation Date: 02 May 2017 16:01:53 UTC
Encoders:  Ryan Gutenkunst
   Alyssa Fortier
   Niloufar Mollasalehi
   Anoop Hunjan
   janet Courtright
   Kevin Gee
set #1
bqbiol:hasProperty Gene Ontology dopamine receptor signaling pathway
Gene Ontology G-protein coupled receptor activity
Gene Ontology dopamine uptake
Gene Ontology adenylate cyclase activity
Mathematical Modelling Ontology MAMO_0000046
bqbiol:hasTaxon Taxonomy Mus musculus
Notes
Nair2015 - Interaction between neuromodulators via GPCRs - Effect on cAMP/PKA signaling (D2 Neuron)

This model is described in the article:

Nair AG, Gutierrez-Arenas O, Eriksson O, Vincent P, Hellgren Kotaleski J.
J. Neurosci. 2015 Oct; 35(41): 14017-14030

Abstract:

Transient changes in striatal dopamine (DA) concentration are considered to encode a reward prediction error (RPE) in reinforcement learning tasks. Often, a phasic DA change occurs concomitantly with a dip in striatal acetylcholine (ACh), whereas other neuromodulators, such as adenosine (Adn), change slowly. There are abundant adenylyl cyclase (AC) coupled GPCRs for these neuromodulators in striatal medium spiny neurons (MSNs), which play important roles in plasticity. However, little is known about the interaction between these neuromodulators via GPCRs. The interaction between these transient neuromodulator changes and the effect on cAMP/PKA signaling via Golf- and Gi/o-coupled GPCR are studied here using quantitative kinetic modeling. The simulations suggest that, under basal conditions, cAMP/PKA signaling could be significantly inhibited in D1R+ MSNs via ACh/M4R/Gi/o and an ACh dip is required to gate a subset of D1R/Golf-dependent PKA activation. Furthermore, the interaction between ACh dip and DA peak, via D1R and M4R, is synergistic. In a similar fashion, PKA signaling in D2+ MSNs is under basal inhibition via D2R/Gi/o and a DA dip leads to a PKA increase by disinhibiting A2aR/Golf, but D2+ MSNs could also respond to the DA peak via other intracellular pathways. This study highlights the similarity between the two types of MSNs in terms of high basal AC inhibition by Gi/o and the importance of interactions between Gi/o and Golf signaling, but at the same time predicts differences between them with regard to the sign of RPE responsible for PKA activation.Dopamine transients are considered to carry reward-related signal in reinforcement learning. An increase in dopamine concentration is associated with an unexpected reward or salient stimuli, whereas a decrease is produced by omission of an expected reward. Often dopamine transients are accompanied by other neuromodulatory signals, such as acetylcholine and adenosine. We highlight the importance of interaction between acetylcholine, dopamine, and adenosine signals via adenylyl-cyclase coupled GPCRs in shaping the dopamine-dependent cAMP/PKA signaling in striatal neurons. Specifically, a dopamine peak and an acetylcholine dip must interact, via D1 and M4 receptor, and a dopamine dip must interact with adenosine tone, via D2 and A2a receptor, in direct and indirect pathway neurons, respectively, to have any significant downstream PKA activation.

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.

Model
Publication ID: 26468202 Submission Date: 20 Feb 2015 11:19:40 UTC Last Modification Date: 16 May 2017 13:20:10 UTC Creation Date: 02 May 2017 16:01:53 UTC
Mathematical expressions
Reactions
revreaction_1 revreaction_2 revreaction_3 revreaction_4
revreaction_5 revreaction_6 revreaction_7 revreaction_8
revreaction_9 revreaction_10 revreaction_11 revreaction_12
revreaction_13 revreaction_14 revreaction_15 revreaction_16
revreaction_17 revreaction_18 revreaction_19 revreaction_20
revreaction_21 revreaction_22 revreaction_23 revreaction_24
revreaction_25 revreaction_26 revreaction_27 revreaction_28
revreaction_29 revreaction_30 revreaction_31 revreaction_32
revreaction_33 revreaction_34 revreaction_35 revreaction_36
revreaction_37 revreaction_38 revreaction_39 revreaction_40
revreaction_41 revreaction_42 revreaction_43 revreaction_44
revreaction_45 revreaction_46 revreaction_47 revreaction_48
revreaction_49 revreaction_50 revreaction_51 revreaction_52
revreaction_53 revreaction_54 revreaction_55 revreaction_56
revreaction_57 revreaction_58 revreaction_59 revreaction_60
revreaction_61 irrevreaction_1 irrevreaction_2 irrevreaction_3
irrevreaction_4 irrevreaction_5 irrevreaction_6 irrevreaction_7
irrevreaction_8 irrevreaction_9 irrevreaction_10 irrevreaction_11
irrevreaction_12 irrevreaction_13 irrevreaction_14 irrevreaction_15
irrevreaction_16 irrevreaction_17 irrevreaction_18 irrevreaction_19
irrevreaction_20 irrevreaction_21 irrevreaction_22 irrevreaction_23
irrevreaction_24 irrevreaction_25 irrevreaction_26 irrevreaction_27
irrevreaction_28 irrevreaction_29 irrevreaction_30 irrevreaction_31
irrevreaction_32 irrevreaction_33 irrevreaction_34 irrevreaction_35
irrevreaction_36 irrevreaction_37 irrevreaction_38 irrevreaction_39
irrevreaction_40 irrevreaction_41 irrevreaction_42 irrevreaction_43
irrevreaction_44 irrevreaction_45 irrevreaction_46 irrevreaction_47
irrevreaction_48 irrevreaction_49 irrevreaction_50 irrevreaction_51
irrevreaction_52      
Rules
Assignment Rule (variable: totalActivePKA) Assignment Rule (variable: DAdip) Assignment Rule (variable: DApeak) Assignment Rule (variable: DA)
Assignment Rule (variable: Adnpeak_tmax) Assignment Rule (variable: Adnpeak_normalize) Assignment Rule (variable: Adnpeak) Assignment Rule (variable: Adn)
Physical entities
Compartments Species
Spine GaiGTP GaolfGDP Gbgolf
GaolfGTP Golf A2ARGolf
cAMP Ca AC5
AC5GaolfGTP CaM CaMCa2
CaMCa4 PDE4 PKA
PKAcAMP2 PKAcAMP4 PKAreg
PKAc PP2B PP2Bc
PP2BCaM PP2BCaMCa2 DARPP32
PKAc*D32 D32p34 B72PP2A
PKAc*B56PP2A B56PP2Ap CDK5
PP1 CDK5*D32 D32p75
PKAcD32p75 B72PPA2Ca B56PP2Ap*D32p75
B72PP2A*D32p75 B72PP2ACa*D32p75 PP1D32p34
PP2Bc*D32p34 B72PP2A*D32p34 Adn
AMP AC5Ca AC5CaGaolfGTP
AC5GaiGTP AC5CaGaiGTP B56PP2A
B56PP2A*D32p75 B72PP2ACa*D32p34 PDE4*cAMP
AC5GaolfGTPGaiGTP AC5CaGaolfGTPGaiGTP D2R
D2RDA D2RGi Gi
D2RDAGi Gbgi GaiGDP
DA PDE10c PDE10
PDE10*cAMP PDE10c*cAMP ATP
AC5GaolfGTPGaiGTP*ATP AC5GaiGTP*ATP AC5GaolfGTP*ATP
AC5*ATP AC5CaGaolfGTP*ATP AC5CaGaiGTP*ATP
AC5CaGaolfGTPGaiGTP*ATP AC5Ca*ATP A2ARAdnGolf
A2ARAdn A2AR totalActivePKA
Global parameters
krD2R*Gi kfD2R*Gi krPP2B*CaMCa2 kfPP2B*CaMCa2
krPP2BCaMCa2*2Ca kfPP2BCaMCa2*2Ca krPP2BCaM*2Ca kfPP2BCaM*2Ca
kfPP1*D32p34 krPP1*D32p34 kfPP2B*CaMCa4 krPP2B*CaMCa4
kfB72PP2A*Ca krB72PP2A*Ca kfPP2B*CaM krPP2B*CaM
kcatPKAc*D32 kGaolfGTPase kfPP2Bc*D32p34 krPP2Bc*D32p34
kfB56PP2A*D32p75 krB56PP2A*D32p75 kfB56PP2Ap*D32p75 krB56PP2Ap*D32p75
kcatB56PP2Ap*D32p75 kcatB56PP2A*D32p75 kcatB72PP2ACa*D32p75 kcatB72PP2A*D32p75
kfB72PP2A*D32p75 krB72PP2A*D32p75 kfB72PP2ACa*D32p75 krB72PP2ACa*D32p75
kcatPP2Bc*D32p34 kcatCDK5*D32 kactGi kGiGTPase
kGiback kfD2RDA*Gi krD2RDA*Gi kfPKA*2cAMP
krPKA*2cAMP krPKAc*PKAr kfPKAc*PKAr kfPKA2cAMP*2cAMP
krPKA2cAMP*2cAMP kfCDK5*D32 krCDK5*D32 kactGolf
kcatPDE4*cAMP kfPKAc*D32 krPKAc*D32 kfPDE4*cAMP
krPDE4*cAMP krPDE10*cAMP kcatPDE10c*cAMP kfPDE10*cAMP
kfcAMP*PDE10 krcAMP*PDE10 kcatcAMP*PDE10 kcatAC5GaolfGTP*ATP
kicatAC5GaolfGTP*ATP kcatAC5*ATP kicatAC5*ATP kcatAC5GaiGTP*ATP
kicatAC5GaiGTP*ATP kcatAC5CaGaiGTP*ATP kicatAC5CaGaiGTP*ATP kcatAC5Ca*ATP
kicatAC5Ca*ATP kcatAC5CaGaolfGTP*ATP kicatAC5CaGaolfGTP*ATP kfD2R*DA
kfD2RGi*DA krD2RGi*DA krD2R*DA kcatAC5GaolfGTPGaiGTP*ATP
kicatAC5GaolfGTPGaiGTP*ATP kicatAC5CaGaolfGTPGaiGTP*ATP kcatAC5CaGaolfGTPGaiGTP*ATP kfAC5*ATP
kfAC5CaGaolfGTP*ATP kfAC5CaGaiGTP*ATP kfAC5CaGaolfGTPGaiGTP*ATP kfCaM*2Ca
kGolfback krCaM*2Ca kdpB56PP2Ap krCaMCa2*2Ca
krPKAc*D32p75 kfPKAc*B56PP2A krPKAc*B56PP2A kfCaMCa2*2Ca
kcatPKAc*B56PP2A kfPKAc*D32p75 kfAC5GaolfGTP*ATP kfAC5GaiGTP*ATP
kfAC5GaolfGTPGaiGTP*ATP kfAC5Ca*ATP kfA2AR*Golf krA2AR*Golf
kfA2ARAdn*Golf krA2ARAdn*Golf kfB72PP2A*D32p34 krB72PP2A*D32p34
krAC5X*ATP kcatB72PP2A*D32p34 kfAC5XGaolfGTP kfAC5Ca
kfAC5XGaiGTP kfAC5XNCGaiGTP kfAC5XNCGaolfGTP krAC5XGaolfGTP
krAC5Ca krAC5XGaiGTP krAC5XNCGaiGTP krAC5XNCGaolfGTP
krgso krgsi kfPDE10c*cAMP krPDE10c*cAMP
kfA2AR*Adn kfA2ARGolf*Adn krA2AR*Adn krA2ARGolf*Adn
DAdip_present DAdip_steepness DAdip_minimum DAdip_maximum
DAdip_startTime DAdip_duration DAdip DApeak_present
DApeak_steepness DApeak_minimum DApeak_maximum DApeak_startTime
DApeak_duration DApeak DA_basal Adn_basal
Adnpeak_maximum Adnpeak_k1 Adnpeak_k2 Adnpeak
Adnpeak_tmax Adnpeak_normalize Adnpeak_startTime Adnpeak_present
Initial for Adn_basal Initial for Adnpeak_k1 Initial for Adnpeak_k2 Initial for Adnpeak_maximum
Initial for Adnpeak_normalize Initial for Adnpeak_present Initial for Adnpeak_startTime Initial for Adnpeak_tmax
Initial for DA_basal Initial for DAdip_duration Initial for DAdip_maximum Initial for DAdip_minimum
Initial for DAdip_present Initial for DAdip_startTime Initial for DAdip_steepness Initial for DApeak_duration
Initial for DApeak_maximum Initial for DApeak_minimum Initial for DApeak_present Initial for DApeak_startTime
Initial for DApeak_steepness      
Reactions (113)
 
 revreaction_1 [A2ARGolf] + [Adn] ↔ [A2ARAdnGolf];  
 
 revreaction_2 [A2ARAdn] + [Golf] ↔ [A2ARAdnGolf];  
 
 revreaction_3 [A2AR] + [Golf] ↔ [A2ARGolf];  
 
 revreaction_4 [A2AR] + [Adn] ↔ [A2ARAdn];  
 
 revreaction_5 [D2R] + [Gi] ↔ [D2RGi];  
 
 revreaction_6 [D2RDA] + [Gi] ↔ [D2RDAGi];  
 
 revreaction_7 [DA] + [D2RGi] ↔ [D2RDAGi];  
 
 revreaction_8 [DA] + [D2R] ↔ [D2RDA];  
 
 revreaction_9 [AC5] + [GaolfGTP] ↔ [AC5GaolfGTP];  
 
 revreaction_10 [AC5] + [Ca] ↔ [AC5Ca];  
 
 revreaction_11 [AC5Ca] + [GaolfGTP] ↔ [AC5CaGaolfGTP];  
 
 revreaction_12 [GaiGTP] + [AC5Ca] ↔ [AC5CaGaiGTP];  
 
 revreaction_13 [GaiGTP] + [AC5] ↔ [AC5GaiGTP];  
 
 revreaction_14 [GaiGTP] + [AC5GaolfGTP] ↔ [AC5GaolfGTPGaiGTP];  
 
 revreaction_15 [GaiGTP] + [AC5CaGaolfGTP] ↔ [AC5CaGaolfGTPGaiGTP];  
 
 revreaction_16 [AC5GaiGTP] + [GaolfGTP] ↔ [AC5GaolfGTPGaiGTP];  
 
 revreaction_17 [AC5CaGaiGTP] + [GaolfGTP] ↔ [AC5CaGaolfGTPGaiGTP];  
 
 revreaction_18 [AC5GaolfGTPGaiGTP] + [ATP] ↔ [AC5GaolfGTPGaiGTP*ATP];  
 
 revreaction_19 [ATP] + [AC5GaiGTP] ↔ [AC5GaiGTP*ATP];  
 
 revreaction_20 [AC5GaolfGTP] + [ATP] ↔ [AC5GaolfGTP*ATP];  
 
 revreaction_21 [AC5] + [ATP] ↔ [AC5*ATP];  
 
 revreaction_22 [AC5Ca] + [ATP] ↔ [AC5Ca*ATP];  
 
 revreaction_23 [AC5CaGaolfGTP] + [ATP] ↔ [AC5CaGaolfGTP*ATP];  
 
 revreaction_24 [AC5CaGaiGTP] + [ATP] ↔ [AC5CaGaiGTP*ATP];  
 
 revreaction_25 [AC5CaGaolfGTPGaiGTP] + [ATP] ↔ [AC5CaGaolfGTPGaiGTP*ATP];  
 
 revreaction_26 [GaolfGTP] + [AC5GaiGTP*ATP] ↔ [AC5GaolfGTPGaiGTP*ATP];  
 
 revreaction_27 [GaolfGTP] + [AC5CaGaiGTP*ATP] ↔ [AC5CaGaolfGTPGaiGTP*ATP];  
 
 revreaction_28 [GaolfGTP] + [AC5*ATP] ↔ [AC5GaolfGTP*ATP];  
 
 revreaction_29 [GaolfGTP] + [AC5Ca*ATP] ↔ [AC5CaGaolfGTP*ATP];  
 
 revreaction_30 [Ca] + [AC5*ATP] ↔ [AC5Ca*ATP];  
 
 revreaction_31 [AC5*ATP] + [GaiGTP] ↔ [AC5GaiGTP*ATP];  
 
 revreaction_32 [GaiGTP] + [AC5GaolfGTP*ATP] ↔ [AC5GaolfGTPGaiGTP*ATP];  
 
 revreaction_33 [AC5Ca*ATP] + [GaiGTP] ↔ [AC5CaGaiGTP*ATP];  
 
 revreaction_34 [GaiGTP] + [AC5CaGaolfGTP*ATP] ↔ [AC5CaGaolfGTPGaiGTP*ATP];  
 
 revreaction_35 [cAMP] + [PKA] ↔ [PKAcAMP2];  
 
 revreaction_36 [cAMP] + [PKAcAMP2] ↔ [PKAcAMP4];  
 
 revreaction_37 [PKAcAMP4] ↔ [PKAc] + [PKAreg];  
 
 revreaction_38 [cAMP] + [PDE4] ↔ [PDE4*cAMP];  
 
 revreaction_39 [PDE10] + 2.0 × [cAMP] ↔ [PDE10c];  
 
 revreaction_40 [cAMP] + [PDE10] ↔ [PDE10*cAMP];  
 
 revreaction_41 [cAMP] + [PDE10c] ↔ [PDE10c*cAMP];  
 
 revreaction_42 [CaM] + [Ca] ↔ [CaMCa2];  
 
 revreaction_43 [Ca] + [CaMCa2] ↔ [CaMCa4];  
 
 revreaction_44 [PP2B] + [CaM] ↔ [PP2BCaM];  
 
 revreaction_45 [PP2B] + [CaMCa4] ↔ [PP2Bc];  
 
 revreaction_46 [PP2BCaM] + [Ca] ↔ [PP2BCaMCa2];  
 
 revreaction_47 [PP2BCaMCa2] + [Ca] ↔ [PP2Bc];  
 
 revreaction_48 [PP2B] + [CaMCa2] ↔ [PP2BCaMCa2];  
 
 revreaction_49 [B72PP2A] + [Ca] ↔ [B72PPA2Ca];  
 
 revreaction_50 [PKAc] + [DARPP32] ↔ [PKAc*D32];  
 
 revreaction_51 [PKAc] + [B56PP2A] ↔ [PKAc*B56PP2A];  
 
 revreaction_52 [D32p34] + [PP1] ↔ [PP1D32p34];  
 
 revreaction_53 [CDK5] + [DARPP32] ↔ [CDK5*D32];  
 
 revreaction_54 [D32p75] + [PKAc] ↔ [PKAcD32p75];  
 
 revreaction_55 [B56PP2Ap] + [D32p75] ↔ [B56PP2Ap*D32p75];  
 
 revreaction_56 [B72PP2A] + [D32p75] ↔ [B72PP2A*D32p75];  
 
 revreaction_57 [D32p75] + [B72PPA2Ca] ↔ [B72PP2ACa*D32p75];  
 
 revreaction_58 [D32p34] + [PP2Bc] ↔ [PP2Bc*D32p34];  
 
 revreaction_59 [D32p75] + [B56PP2A] ↔ [B56PP2A*D32p75];  
 
 revreaction_60 [D32p34] + [B72PPA2Ca] ↔ [B72PP2ACa*D32p34];  
 
 revreaction_61 [D32p34] + [B72PP2A] ↔ [B72PP2A*D32p34];  
 
 irrevreaction_1 [A2ARAdnGolf] → [Gbgolf] + [A2ARAdn] + [GaolfGTP];  
 
 irrevreaction_2 [GaolfGTP] → [GaolfGDP];  
 
 irrevreaction_3 [GaolfGDP] + [Gbgolf] → [Golf];  
 
 irrevreaction_4 [D2RDAGi] → [GaiGTP] + [D2RDA] + [Gbgi];  
 
 irrevreaction_5 [GaiGTP] → [GaiGDP];  
 
 irrevreaction_6 [Gbgi] + [GaiGDP] → [Gi];  
 
 irrevreaction_7 [AC5GaolfGTP*ATP] → [cAMP] + [AC5GaolfGTP];  
 
 irrevreaction_8 [cAMP] + [AC5GaolfGTP] → [AC5GaolfGTP*ATP];  
 
 irrevreaction_9 [AC5*ATP] → [cAMP] + [AC5];  
 
 irrevreaction_10 [cAMP] + [AC5] → [AC5*ATP];  
 
 irrevreaction_11 [AC5GaiGTP*ATP] → [cAMP] + [AC5GaiGTP];  
 
 irrevreaction_12 [cAMP] + [AC5GaiGTP] → [AC5GaiGTP*ATP];  
 
 irrevreaction_13 [AC5GaolfGTPGaiGTP*ATP] → [cAMP] + [AC5GaolfGTPGaiGTP];  
 
 irrevreaction_14 [cAMP] + [AC5GaolfGTPGaiGTP] → [AC5GaolfGTPGaiGTP*ATP];  
 
 irrevreaction_15 [AC5CaGaolfGTPGaiGTP*ATP] → [cAMP] + [AC5CaGaolfGTPGaiGTP];  
 
 irrevreaction_16 [cAMP] + [AC5CaGaolfGTPGaiGTP] → [AC5CaGaolfGTPGaiGTP*ATP];  
 
 irrevreaction_17 [AC5CaGaiGTP*ATP] → [cAMP] + [AC5CaGaiGTP];  
 
 irrevreaction_18 [cAMP] + [AC5CaGaiGTP] → [AC5CaGaiGTP*ATP];  
 
 irrevreaction_19 [AC5Ca*ATP] → [cAMP] + [AC5Ca];  
 
 irrevreaction_20 [cAMP] + [AC5Ca] → [AC5Ca*ATP];  
 
 irrevreaction_21 [AC5CaGaolfGTP*ATP] → [cAMP] + [AC5CaGaolfGTP];  
 
 irrevreaction_22 [cAMP] + [AC5CaGaolfGTP] → [AC5CaGaolfGTP*ATP];  
 
 irrevreaction_23 [AC5GaolfGTP] → [AC5] + [GaolfGDP];  
 
 irrevreaction_24 [AC5CaGaolfGTP] → [AC5Ca] + [GaolfGDP];  
 
 irrevreaction_25 [AC5CaGaiGTP] → [AC5Ca] + [GaiGDP];  
 
 irrevreaction_26 [AC5GaiGTP] → [AC5] + [GaiGDP];  
 
 irrevreaction_27 [AC5GaolfGTPGaiGTP] → [AC5GaiGTP] + [GaolfGDP];  
 
 irrevreaction_28 [AC5GaolfGTPGaiGTP] → [AC5GaolfGTP] + [GaiGDP];  
 
 irrevreaction_29 [AC5CaGaolfGTPGaiGTP] → [AC5CaGaiGTP] + [GaolfGDP];  
 
 irrevreaction_30 [AC5CaGaolfGTPGaiGTP] → [AC5CaGaolfGTP] + [GaiGDP];  
 
 irrevreaction_31 [AC5GaolfGTPGaiGTP*ATP] → [GaiGDP] + [AC5GaolfGTP*ATP];  
 
 irrevreaction_32 [AC5GaiGTP*ATP] → [AC5*ATP] + [GaiGDP];  
 
 irrevreaction_33 [AC5GaolfGTPGaiGTP*ATP] → [AC5GaiGTP*ATP] + [GaolfGDP];  
 
 irrevreaction_34 [AC5GaolfGTP*ATP] → [AC5*ATP] + [GaolfGDP];  
 
 irrevreaction_35 [AC5CaGaolfGTP*ATP] → [AC5Ca*ATP] + [GaolfGDP];  
 
 irrevreaction_36 [AC5CaGaolfGTPGaiGTP*ATP] → [AC5CaGaolfGTP*ATP] + [GaiGDP];  
 
 irrevreaction_37 [AC5CaGaiGTP*ATP] → [AC5Ca*ATP] + [GaiGDP];  
 
 irrevreaction_38 [AC5CaGaolfGTPGaiGTP*ATP] → [AC5CaGaiGTP*ATP] + [GaolfGDP];  
 
 irrevreaction_39 [PDE4*cAMP] → [PDE4] + [AMP];  
 
 irrevreaction_40 [PDE10*cAMP] → [PDE10] + [AMP];  
 
 irrevreaction_41 [PDE10c*cAMP] → [PDE10c] + [AMP];  
 
 irrevreaction_42 [PKAc*D32] → [D32p34] + [PKAc];  
 
 irrevreaction_43 [PKAc*B56PP2A] → [B56PP2Ap] + [PKAc];  
 
 irrevreaction_44 [B56PP2Ap] → [B56PP2A];  
 
 irrevreaction_45 [CDK5*D32] → [CDK5] + [D32p75];  
 
 irrevreaction_46 [B56PP2Ap*D32p75] → [B56PP2Ap] + [DARPP32];  
 
 irrevreaction_47 [B72PP2A*D32p75] → [B72PP2A] + [DARPP32];  
 
 irrevreaction_48 [B72PP2ACa*D32p75] → [B72PPA2Ca] + [DARPP32];  
 
 irrevreaction_49 [B56PP2A*D32p75] → [B56PP2A] + [DARPP32];  
 
 irrevreaction_50 [B72PP2ACa*D32p34] → [B72PPA2Ca] + [DARPP32];  
 
 irrevreaction_51 [B72PP2A*D32p34] → [DARPP32] + [B72PP2A];  
 
 irrevreaction_52 [PP2Bc*D32p34] → [DARPP32] + [PP2Bc];  
 
Rules (8)
 
 Assignment Rule (name: totalActivePKA) totalActivePKA = mwcfcf2e7f_907a_4d25_812f_6c10a7293859-mwb320746f_6a8c_4c8b_ae55_23db454339d8
 
 Assignment Rule (name: DAdip) DAdip = ModelValue_126+(ModelValue_127-ModelValue_126)*((1-1/(1+exp((-ModelValue_125)*time+ModelValue_125*ModelValue_128)))+1/(1+exp((-ModelValue_125)*time+ModelValue_125*(ModelValue_128+ModelValue_129))))
 
 Assignment Rule (name: DApeak) DApeak = ModelValue_133+(ModelValue_134-ModelValue_133)*(1/(1+exp((-ModelValue_132)*time+ModelValue_132*ModelValue_135))-1/(1+exp((-ModelValue_132)*time+ModelValue_132*(ModelValue_135+ModelValue_136))))
 
 Assignment Rule (name: mw3e1a2fbf_37b1_490c_9528_6cb6bbf11b21) DA = ((1-ModelValue_124)-ModelValue_131)*ModelValue_138+ModelValue_124*DAdip+ModelValue_131*DApeak
 
 Assignment Rule (name: Adnpeak_tmax) Adnpeak_tmax = ln(ModelValue_141/ModelValue_142)/(ModelValue_141-ModelValue_142)
 
 Assignment Rule (name: Adnpeak_normalize) Adnpeak_normalize = exp((-ModelValue_141)*ModelValue_144)-exp((-ModelValue_142)*ModelValue_144)
 
 Assignment Rule (name: Adnpeak) Adnpeak = piecewise(0, time < ModelValue_146, (exp((-ModelValue_141)*(time-ModelValue_146))-exp((-ModelValue_142)*(time-ModelValue_146)))/ModelValue_145)
 
 Assignment Rule (name: mwbe974953_e869_4622_b4a8_745555c8d7fd) Adn = ModelValue_139+ModelValue_147*(ModelValue_140-ModelValue_139)*Adnpeak
 
 Spine Spatial dimensions: 3.0  Compartment size: 1.0E-15
 
 GaiGTP
Compartment: Spine
Initial concentration: 101.537255319083
 
 GaolfGDP
Compartment: Spine
Initial concentration: 0.0531637942417174
 
 Gbgolf
Compartment: Spine
Initial concentration: 238.130359192413
 
 GaolfGTP
Compartment: Spine
Initial concentration: 40.5536821102806
 
 Golf
Compartment: Spine
Initial concentration: 558.982542555614
 
 A2ARGolf
Compartment: Spine
Initial concentration: 360.687386864497
 
 cAMP
Compartment: Spine
Initial concentration: 174.626297500174
 
 Ca
Compartment: Spine
Initial concentration: 60.0
Constant
 
 AC5
Compartment: Spine
Initial concentration: 0.0128710191542525
 
 AC5GaolfGTP
Compartment: Spine
Initial concentration: 0.70701857780577
 
 CaM
Compartment: Spine
Initial concentration: 5761.94480051912
 
 CaMCa2
Compartment: Spine
Initial concentration: 249.610539967081
 
 CaMCa4
Compartment: Spine
Initial concentration: 2.66057727607432
 
 PDE4
Compartment: Spine
Initial concentration: 1264.15245670154
 
 PKA
Compartment: Spine
Initial concentration: 1046.38537747111
 
 PKAcAMP2
Compartment: Spine
Initial concentration: 47.508865098789
 
 PKAcAMP4
Compartment: Spine
Initial concentration: 2.87051883488477
 
 PKAreg
Compartment: Spine
Initial concentration: 103.235238595214
 
 PKAc
Compartment: Spine
Initial concentration: 11.1222442024494
 
 PP2B
Compartment: Spine
Initial concentration: 14.2159177622785
 
 PP2Bc
Compartment: Spine
Initial concentration: 400.245527991333
 
 PP2BCaM
Compartment: Spine
Initial concentration: 2723.80592164809
 
 PP2BCaMCa2
Compartment: Spine
Initial concentration: 860.894886021872
 
 DARPP32
Compartment: Spine
Initial concentration: 36783.7008751031
 
 PKAc*D32
Compartment: Spine
Initial concentration: 2.27287391001524
 
 D32p34
Compartment: Spine
Initial concentration: 3.34893066516414
 
 B72PP2A
Compartment: Spine
Initial concentration: 285.044742516553
 
 PKAc*B56PP2A
Compartment: Spine
Initial concentration: 49.4641285880295
 
 B56PP2Ap
Compartment: Spine
Initial concentration: 824.402142986414
 
 CDK5
Compartment: Spine
Initial concentration: 236.187426115463
 
 PP1
Compartment: Spine
Initial concentration: 373.906510515608
 
 CDK5*D32
Compartment: Spine
Initial concentration: 1563.81257388454
 
 D32p75
Compartment: Spine
Initial concentration: 9811.3564538487
 
 PKAcD32p75
Compartment: Spine
Initial concentration: 40.3759918947167
 
 B72PPA2Ca
Compartment: Spine
Initial concentration: 17.1026845509875
 
 B56PP2Ap*D32p75
Compartment: Spine
Initial concentration: 449.361293675004
 
 B72PP2A*D32p75
Compartment: Spine
Initial concentration: 302.34330531086
 
 B72PP2ACa*D32p75
Compartment: Spine
Initial concentration: 11.1867022960323
 
 PP1D32p34
Compartment: Spine
Initial concentration: 626.093489484392
 
 PP2Bc*D32p34
Compartment: Spine
Initial concentration: 0.837746576428105
 
 B72PP2A*D32p34
Compartment: Spine
Initial concentration: 79.5495899297818
 
  Adn
Compartment: Spine
Initial concentration: 150.0
 
 AMP
Compartment: Spine
Initial concentration: 0.0
Constant
 
 AC5Ca
Compartment: Spine
Initial concentration: 8.58515661313367E-4
 
 AC5CaGaolfGTP
Compartment: Spine
Initial concentration: 0.0472000651727838
 
 AC5GaiGTP
Compartment: Spine
Initial concentration: 1.86281966630368
 
 AC5CaGaiGTP
Compartment: Spine
Initial concentration: 0.124257816126398
 
 B56PP2A
Compartment: Spine
Initial concentration: 355.78523672509
 
 B56PP2A*D32p75
Compartment: Spine
Initial concentration: 320.987198025465
 
 B72PP2ACa*D32p34
Compartment: Spine
Initial concentration: 4.77297539578531
 
 PDE4*cAMP
Compartment: Spine
Initial concentration: 735.847543298457
 
 AC5GaolfGTPGaiGTP
Compartment: Spine
Initial concentration: 0.0287554044888205
 
 AC5CaGaolfGTPGaiGTP
Compartment: Spine
Initial concentration: 0.00191770645875004
 
 D2R
Compartment: Spine
Initial concentration: 1178.62868437996
 
 D2RDA
Compartment: Spine
Initial concentration: 7.56233567943301
 
 D2RGi
Compartment: Spine
Initial concentration: 509.673857745172
 
 Gi
Compartment: Spine
Initial concentration: 1577.62092309684
 
 D2RDAGi
Compartment: Spine
Initial concentration: 304.135122195432
 
 Gbgi
Compartment: Spine
Initial concentration: 608.570096962554
 
 GaiGDP
Compartment: Spine
Initial concentration: 0.299852185311676
 
  DA
Compartment: Spine
Initial concentration: 10.0
 
 PDE10c
Compartment: Spine
Initial concentration: 0.752558093764585
 
 PDE10
Compartment: Spine
Initial concentration: 222.10751256206
 
 PDE10*cAMP
Compartment: Spine
Initial concentration: 775.716251313715
 
 PDE10c*cAMP
Compartment: Spine
Initial concentration: 1.42367803045989
 
 ATP
Compartment: Spine
Initial concentration: 5000000.0
Constant
 
 AC5GaolfGTPGaiGTP*ATP
Compartment: Spine
Initial concentration: 7.19411431239488
 
 AC5GaiGTP*ATP
Compartment: Spine
Initial concentration: 465.976488232566
 
 AC5GaolfGTP*ATP
Compartment: Spine
Initial concentration: 177.248405413735
 
 AC5*ATP
Compartment: Spine
Initial concentration: 3.21952737331881
 
 AC5CaGaolfGTP*ATP
Compartment: Spine
Initial concentration: 11.8164948664804
 
 AC5CaGaiGTP*ATP
Compartment: Spine
Initial concentration: 31.0650293784667
 
 AC5CaGaolfGTPGaiGTP*ATP
Compartment: Spine
Initial concentration: 0.479606941354312
 
 AC5Ca*ATP
Compartment: Spine
Initial concentration: 0.214634710512781
 
 A2ARAdnGolf
Compartment: Spine
Initial concentration: 42.199711387476
 
 A2ARAdn
Compartment: Spine
Initial concentration: 386.371717183793
 
 A2AR
Compartment: Spine
Initial concentration: 210.741184564234
 
  totalActivePKA
Compartment: Spine
Initial concentration: 62.8592467004969
 
Global Parameters (169)
 
   krD2R*Gi
Value: 200.0
Constant
 
   kfD2R*Gi
Value: 0.055
Constant
 
   krPP2B*CaMCa2
Value: 3.0
Constant
 
   kfPP2B*CaMCa2
Value: 1.0
Constant
 
   krPP2BCaMCa2*2Ca
Value: 10.0
Constant
 
   kfPP2BCaMCa2*2Ca
Value: 0.1
Constant
 
   krPP2BCaM*2Ca
Value: 0.91
Constant
 
   kfPP2BCaM*2Ca
Value: 0.006
Constant
 
   kfPP1*D32p34
Value: 0.02
Constant
 
   krPP1*D32p34
Value: 0.04
Constant
 
   kfPP2B*CaMCa4
Value: 1.0
Constant
 
   krPP2B*CaMCa4
Value: 3.0
Constant
 
   kfB72PP2A*Ca
Value: 1.0E-4
Constant
 
   krB72PP2A*Ca
Value: 0.1
Constant
 
   kfPP2B*CaM
Value: 1.0
Constant
 
   krPP2B*CaM
Value: 30.0
Constant
 
   kcatPKAc*D32
Value: 10.0
Constant
 
   kGaolfGTPase
Value: 30.0
Constant
 
   kfPP2Bc*D32p34
Value: 0.005
Constant
 
   krPP2Bc*D32p34
Value: 1.0
Constant
 
   kfB56PP2A*D32p75
Value: 8.0E-4
Constant
 
   krB56PP2A*D32p75
Value: 6.4
Constant
 
   kfB56PP2Ap*D32p75
Value: 0.001
Constant
 
   krB56PP2Ap*D32p75
Value: 10.0
Constant
 
   kcatB56PP2Ap*D32p75
Value: 8.0
Constant
 
   kcatB56PP2A*D32p75
Value: 2.3
Constant
 
   kcatB72PP2ACa*D32p75
Value: 5.0
Constant
 
   kcatB72PP2A*D32p75
Value: 1.0
Constant
 
   kfB72PP2A*D32p75
Value: 8.0E-4
Constant
 
   krB72PP2A*D32p75
Value: 6.4
Constant
 
   kfB72PP2ACa*D32p75
Value: 0.001
Constant
 
   krB72PP2ACa*D32p75
Value: 10.0
Constant
 
   kcatPP2Bc*D32p34
Value: 7.0
Constant
 
   kcatCDK5*D32
Value: 3.0
Constant
 
 kactGi
Value: 60.0
Constant
 
 kGiGTPase
Value: 30.0
Constant
 
   kGiback
Value: 100.0
Constant
 
   kfD2RDA*Gi
Value: 6.6
Constant
 
   krD2RDA*Gi
Value: 200.0
Constant
 
   kfPKA*2cAMP
Value: 2.6E-4
Constant
 
   krPKA*2cAMP
Value: 1.0
Constant
 
   krPKAc*PKAr
Value: 10.0
Constant
 
   kfPKAc*PKAr
Value: 0.025
Constant
 
   kfPKA2cAMP*2cAMP
Value: 3.46E-4
Constant
 
   krPKA2cAMP*2cAMP
Value: 1.0
Constant
 
   kfCDK5*D32
Value: 9.0E-4
Constant
 
   krCDK5*D32
Value: 2.0
Constant
 
 kactGolf
Value: 30.0
Constant
 
   kcatPDE4*cAMP
Value: 2.0
Constant
 
   kfPKAc*D32
Value: 1.0E-4
Constant
 
   krPKAc*D32
Value: 8.0
Constant
 
   kfPDE4*cAMP
Value: 0.01
Constant
 
   krPDE4*cAMP
Value: 1.0
Constant
 
   krPDE10*cAMP
Value: 9.0
Constant
 
   kcatPDE10c*cAMP
Value: 10.0
Constant
 
   kfPDE10*cAMP
Value: 1.0E-6
Constant
 
   kfcAMP*PDE10
Value: 0.1
Constant
 
   krcAMP*PDE10
Value: 2.0
Constant
 
   kcatcAMP*PDE10
Value: 3.0
Constant
 
 kcatAC5GaolfGTP*ATP
Value: 20.0
Constant
 
 kicatAC5GaolfGTP*ATP
Value: 0.084
Constant
 
 kcatAC5*ATP
Value: 1.0
Constant
 
 kicatAC5*ATP
Value: 4.0E-4
Constant
 
   kcatAC5GaiGTP*ATP
Value: 0.25
Constant
 
   kicatAC5GaiGTP*ATP
Value: 0.00105
Constant
 
 kcatAC5CaGaiGTP*ATP
Value: 0.125
Constant
 
   kicatAC5CaGaiGTP*ATP
Value: 2.8125E-5
Constant
 
 kcatAC5Ca*ATP
Value: 0.5
Constant
 
   kicatAC5Ca*ATP
Value: 1.5E-4
Constant
 
 kcatAC5CaGaolfGTP*ATP
Value: 10.0
Constant
 
   kicatAC5CaGaolfGTP*ATP
Value: 0.022
Constant
 
 kfD2R*DA
Value: 0.1
Constant
 
   kfD2RGi*DA
Value: 12.0
Constant
 
   krD2RGi*DA
Value: 200.0
Constant
 
   krD2R*DA
Value: 200.0
Constant
 
   kcatAC5GaolfGTPGaiGTP*ATP
Value: 5.0
Constant
 
   kicatAC5GaolfGTPGaiGTP*ATP
Value: 0.006
Constant
 
   kicatAC5CaGaolfGTPGaiGTP*ATP
Value: 0.00175
Constant
 
 kcatAC5CaGaolfGTPGaiGTP*ATP
Value: 2.5
Constant
 
   kfAC5*ATP
Value: 1.0E-4
Constant
 
   kfAC5CaGaolfGTP*ATP
Value: 5.5E-4
Constant
 
   kfAC5CaGaiGTP*ATP
Value: 5.625E-5
Constant
 
   kfAC5CaGaolfGTPGaiGTP*ATP
Value: 1.75E-4
Constant
 
   kfCaM*2Ca
Value: 0.006
Constant
 
   kGolfback
Value: 100.0
Constant
 
   krCaM*2Ca
Value: 9.1
Constant
 
   kdpB56PP2Ap
Value: 0.006
Constant
 
   krCaMCa2*2Ca
Value: 1000.0
Constant
 
   krPKAc*D32p75
Value: 1.0
Constant
 
   kfPKAc*B56PP2A
Value: 0.005
Constant
 
   krPKAc*B56PP2A
Value: 0.3
Constant
 
   kfCaMCa2*2Ca
Value: 0.1
Constant
 
   kcatPKAc*B56PP2A
Value: 0.1
Constant
 
   kfPKAc*D32p75
Value: 3.7E-4
Constant
 
   kfAC5GaolfGTP*ATP
Value: 0.00105
Constant
 
   kfAC5GaiGTP*ATP
Value: 6.25E-5
Constant
 
   kfAC5GaolfGTPGaiGTP*ATP
Value: 3.0E-4
Constant
 
   kfAC5Ca*ATP
Value: 7.5E-5
Constant
 
   kfA2AR*Golf
Value: 0.005
Constant
 
   krA2AR*Golf
Value: 1.0
Constant
 
   kfA2ARAdn*Golf
Value: 0.005
Constant
 
   krA2ARAdn*Golf
Value: 1.0
Constant
 
   kfB72PP2A*D32p34
Value: 0.1
Constant
 
   krB72PP2A*D32p34
Value: 1.0
Constant
 
   krAC5X*ATP
Value: 1.0
Constant
 
   kcatB72PP2A*D32p34
Value: 0.2
Constant
 
   kfAC5XGaolfGTP
Value: 0.2
Constant
 
   kfAC5Ca
Value: 0.001
Constant
 
   kfAC5XGaiGTP
Value: 50.0
Constant
 
   kfAC5XNCGaiGTP
Value: 0.01
Constant
 
   kfAC5XNCGaolfGTP
Value: 0.002
Constant
 
   krAC5XGaolfGTP
Value: 0.1
Constant
 
   krAC5Ca
Value: 0.9
Constant
 
   krAC5XGaiGTP
Value: 5.0
Constant
 
   krAC5XNCGaiGTP
Value: 0.01
Constant
 
   krAC5XNCGaolfGTP
Value: 0.01
Constant
 
   krgso
Value: 0.25
Constant
 
   krgsi
Value: 30.0
Constant
 
   kfPDE10c*cAMP
Value: 0.13
Constant
 
   krPDE10c*cAMP
Value: 2.0
Constant
 
 kfA2AR*Adn
Value: 0.005
Constant
 
   kfA2ARGolf*Adn
Value: 0.005
Constant
 
   krA2AR*Adn
Value: 1.0
Constant
 
   krA2ARGolf*Adn
Value: 1.0
Constant
 
   DAdip_present
Constant
 
   DAdip_steepness
Value: 100.0
Constant
 
 DAdip_minimum
Value: 0.001
Constant
 
 DAdip_maximum
Value: 10.0
Constant
 
   DAdip_startTime
Value: 10.0
Constant
 
   DAdip_duration
Value: 1.0
Constant
 
  DAdip
Value: 10.0
 
 DApeak_present
Constant
 
   DApeak_steepness
Value: 100.0
Constant
 
 DApeak_minimum
Value: 10.0
Constant
 
   DApeak_maximum
Value: 1500.0
Constant
 
   DApeak_startTime
Value: 10.0
Constant
 
   DApeak_duration
Value: 1.0
Constant
 
  DApeak
Value: 10.0
 
   DA_basal
Value: 10.0
Constant
 
 Adn_basal
Value: 150.0
Constant
 
   Adnpeak_maximum
Value: 1000.0
Constant
 
   Adnpeak_k1
Value: 0.01
Constant
 
   Adnpeak_k2
Value: 0.3
Constant
 
  Adnpeak  
 
  Adnpeak_tmax
Value: 11.7282668333178
 
  Adnpeak_normalize
Value: 0.859689312097976
 
   Adnpeak_startTime
Value: 2.0
Constant
 
   Adnpeak_present
Constant
 
 Initial for Adn_basal
Value: 150.0
Constant
 
 Initial for Adnpeak_k1
Value: 0.01
Constant
 
 Initial for Adnpeak_k2
Value: 0.3
Constant
 
 Initial for Adnpeak_maximum
Value: 1000.0
Constant
 
 Initial for Adnpeak_normalize
Value: 0.859689312097976
Constant
 
 Initial for Adnpeak_present
Constant
 
 Initial for Adnpeak_startTime
Value: 2.0
Constant
 
 Initial for Adnpeak_tmax
Value: 11.7282668333178
Constant
 
 Initial for DA_basal
Value: 10.0
Constant
 
 Initial for DAdip_duration
Value: 1.0
Constant
 
 Initial for DAdip_maximum
Value: 10.0
Constant
 
 Initial for DAdip_minimum
Value: 0.001
Constant
 
 Initial for DAdip_present
Constant
 
 Initial for DAdip_startTime
Value: 10.0
Constant
 
 Initial for DAdip_steepness
Value: 100.0
Constant
 
 Initial for DApeak_duration
Value: 1.0
Constant
 
 Initial for DApeak_maximum
Value: 1500.0
Constant
 
 Initial for DApeak_minimum
Value: 10.0
Constant
 
 Initial for DApeak_present
Constant
 
 Initial for DApeak_startTime
Value: 10.0
Constant
 
 Initial for DApeak_steepness
Value: 100.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000636

Curator's comment: (updated: 02 May 2017 16:53:54 BST)

We reproduced figure 5C from the paper using COPASI and created the plot using Matplotlib.

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