Dutta-Roy2015 - Opening of the multiple AMPA receptor conductance states

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Model Identifier
BIOMD0000000569
Short description
Dutta-Roy2015 - Opening of the multiple AMPA receptor conductance states

This model is described in the article:

Dutta-Roy R, Rosenmund C, Edelstein SJ, Le Novère N.
PLoS ONE 2015; 10(1): e0116616

Abstract:

Modulation of the properties of AMPA receptors at the post-synaptic membrane is one of the main suggested mechanisms underlying fast synaptic transmission in the central nervous system of vertebrates. Electrophysiological recordings of single channels stimulated with agonists showed that both recombinant and native AMPA receptors visit multiple conductance states in an agonist concentration dependent manner. We propose an allosteric model of the multiple conductance states based on concerted conformational transitions of the four subunits, as an iris diaphragm. Our model predicts that the thermodynamic behaviour of the conductance states upon full and partial agonist stimulations can be described with increased affinity of receptors as they progress to higher conductance states. The model also predicts the existence of AMPA receptors in non-liganded conductive substates. However, the probability of spontaneous openings decreases with increasing conductances. Finally, we predict that the large conductance states are stabilized within the rise phase of a whole-cell EPSC in glutamatergic hippocampal neurons. Our model provides a mechanistic link between ligand concentration and conductance states that can explain thermodynamic and kinetic features of AMPA receptor gating.

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
  • Ligand-dependent opening of the multiple AMPA receptor conductance states: a concerted model.
  • Dutta-Roy R, Rosenmund C, Edelstein SJ, Le Novère N
  • PloS one , 0/ 2015 , Volume 10 , pages: e0116616 , PubMed ID: 25629405
  • Department of Medicine Solna, Karolinska Insitutet, 171 76 Stockholm, Sweden; NWFZ, Charite Universitatsmedizin, 101 17 Berlin, Germany; European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Modulation of the properties of AMPA receptors at the post-synaptic membrane is one of the main suggested mechanisms underlying fast synaptic transmission in the central nervous system of vertebrates. Electrophysiological recordings of single channels stimulated with agonists showed that both recombinant and native AMPA receptors visit multiple conductance states in an agonist concentration dependent manner. We propose an allosteric model of the multiple conductance states based on concerted conformational transitions of the four subunits, as an iris diaphragm. Our model predicts that the thermodynamic behaviour of the conductance states upon full and partial agonist stimulations can be described with increased affinity of receptors as they progress to higher conductance states. The model also predicts the existence of AMPA receptors in non-liganded conductive substates. However, the probability of spontaneous openings decreases with increasing conductances. Finally, we predict that the large conductance states are stabilized within the rise phase of a whole-cell EPSC in glutamatergic hippocampal neurons. Our model provides a mechanistic link between ligand concentration and conductance states that can explain thermodynamic and kinetic features of AMPA receptor gating.
Contributors
Nicolas Le Novère, administrator

Metadata information

is
BioModels Database MODEL1407160000
BioModels Database BIOMD0000000569
isDescribedBy
PubMed 25629405
hasTaxon
Taxonomy Homo sapiens
isVersionOf

Curation status
Curated

Tags
Name Description Size Actions

Model files

BIOMD0000000569_url.xml SBML L2V4 representation of Dutta-Roy2015 - Opening of the multiple AMPA receptor conductance states 155.48 KB Preview | Download

Additional files

Dutta-Roy2015.cps Copasi file of the model 213.54 KB Preview | Download
BIOMD0000000569-biopax2.owl Auto-generated BioPAX (Level 2) 78.66 KB Preview | Download
BIOMD0000000569.pdf Auto-generated PDF file 458.14 KB Preview | Download
BIOMD0000000569.png Auto-generated Reaction graph (PNG) 1.47 MB Preview | Download
BIOMD0000000569.vcml Auto-generated VCML file 165.19 KB Preview | Download
BIOMD0000000569.xpp Auto-generated XPP file 13.94 KB Preview | Download
BIOMD0000000569.m Auto-generated Octave file 19.20 KB Preview | Download
BIOMD0000000569.svg Auto-generated Reaction graph (SVG) 169.18 KB Preview | Download
BIOMD0000000569.sci Auto-generated Scilab file 10.87 KB Preview | Download
BIOMD0000000569_urn.xml Auto-generated SBML file with URNs 155.31 KB Preview | Download
Morris2008.cps Morris2008.cps 31.90 KB Preview | Download
BIOMD0000000569-biopax3.owl Auto-generated BioPAX (Level 3) 137.75 KB Preview | Download

  • Model originally submitted by : Nicolas Le Novère
  • Submitted: Jul 16, 2014 9:46:54 PM
  • Last Modified: Dec 21, 2018 5:54:36 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Dec 21, 2018 5:54:36 PM
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission: Dutta-Roy2015.cps, Morris2008.cps
  • Version: 2 public model Download this version
    • Submitted on: Apr 8, 2016 6:53:05 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Current version of Dutta-Roy2015 - Opening of the multiple AMPA receptor conductance states
  • Version: 1 public model Download this version
    • Submitted on: Jul 16, 2014 9:46:54 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Original import of AMPAR concerted opening
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
M4 0.0 mol
L0 0.0 mol
L1 0.0 mol
S4 0.0 mol
Reactions
Reactions Rate Parameters
(S4) => (M4)

([S4]) => ([M4])
synapse*SMk4*S4

synapse*SMk4*[S4]
SMk4 = 20000.0
(M4) => (S4)

([M4]) => ([S4])
synapse*MSk4*M4

synapse*MSk4*[M4]
MSk4 = 145.0
(M4) => (L4)

([M4]) => ([L4])
synapse*MLk4*M4

synapse*MLk4*[M4]
MLk4 = 50000.0
(L4) => (M4)

([L4]) => ([M4])
synapse*LMk4*L4

synapse*LMk4*[L4]
LMk4 = 691.0
(M3 + glu) => (M4)

([M3] + [glutamic acid]) => ([M4])
synapse*4*Mkon*M3

synapse*4*Mkon*[M3]
Mkon = 5000000.0
(M4) => (M3 + glu)

([M4]) => ([M3] + [glutamic acid])
synapse*4*Mkoff*M4

synapse*4*Mkoff*[M4]
Mkoff = 16.65
(M0) => (L0)

([M0]) => ([L0])
synapse*MLk0*M0

synapse*MLk0*[M0]
MLk0 = 238.05
(L0) => (M0)

([L0]) => ([M0])
synapse*LMk0*L0

synapse*LMk0*[L0]
LMk0 = 145137.576139466
(L1) => (L0 + glu)

([L1]) => ([L0] + [glutamic acid])
synapse*Lkoff*L1

synapse*Lkoff*[L1]
Lkoff = 1.149
(L1 + glu) => (L2)

([L1] + [glutamic acid]) => ([L2])
synapse*3*Lkon*L1*glu

synapse*3*Lkon*[L1]*[glutamic acid]
Lkon = 5000000.0
(S4) => (B4)

([S4]) => ([B4])
synapse*SBk4*S4

synapse*SBk4*[S4]
SBk4 = 860.0
(S3 + glu) => (S4)

([S3] + [glutamic acid]) => ([S4])
synapse*Skon*S3*glu

synapse*Skon*[S3]*[glutamic acid]
Skon = 5000000.0
(S4) => (S3 + glu)

([S4]) => ([S3] + [glutamic acid])
synapse*4*Skoff*S4

synapse*4*Skoff*[S4]
Skoff = 270.4
Curator's comment:
(added: 23 Mar 2015, 15:27:23, updated: 23 Mar 2015, 15:27:23)
Figure 3B (right) of the reference publication has been reproduced here. Stochastic simulation of a population of 50 receptors for 0.01 seconds. Only the most populated states are represented (and named in the legend) for sake of clarity. Simulation was done using Copasi v4.14 (Build 89) and the plots were generated using Gnuplot. The Copasi file of the model with simulation settings and Matlab files, found as supplementary material in the publication, can be downloaded from the below links: