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The Role of the Glutamate-Glutamine Cycle in Synaptic Transmission During Ischemia and Recovery.

Code ↔ Paper

6 matches between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 6 matches
  1. [1] § Methods › The Model Equations ↔ Dictionary.m, lines 31–45 · score 0.77 · membrane water permeability, universal gas constant, Faraday, moles
  2. [2] § Methods ↔ Dictionary.m, lines 71–125 · score 0.74 · oxygen diffusion, glutamate recycling, oxygen bath, cotransporter, NKCC1, NCX
  3. [3] § Methods ↔ Dictionary.m, lines 71–125 · score 0.67 · oxygen diffusion, glutamate transporter, oxygen bath, cotransporter, NKCC1, NCX
  4. [4] § Results › Glutamate Dynamics During Ischemia › Moderate Ischemia ↔ Plots.m, lines 35–73 · score 0.57 · moderate ischemia, ion concentrations, membrane potentials, potassium, calcium, oxygen
  5. [5] § Results › Glutamate Dynamics During Ischemia › Severe Ischemia ↔ Plots.m, lines 35–73 · score 0.56 · moderate ischemia, ion concentrations, glutamine concentrations, GG, calcium, oxygen
  6. [6] § Methods ↔ Model.m, lines 142–227 · score 0.54 · glutamate cycle, square, duration, KCC, SAT, NCX

Paper

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The authors' code

MATLAB · 197 lines · 8.3 KB · no license · 3 matches

  1. % Creates a dictionary for all constants,parameters
  2. % Written by Hannah van Susteren
  4. function [M] = Dictionary(varargin)
  6. if length(varargin) ==1
  7. varargin = varargin{1};
  8. end
  11. %Put all the default values in a dictionary M.
  12. M = dictionary;
  15. %%
  16. M('tstart') = 0;
  17. M('tend') = 0;
  18. M('time1_OD') = 0;
  19. M('time2_OD') = 0;
  20. M('time1_SB') = 0;
  21. M('time2_SB') = 0;
  22. M('time1_GS') = 0;
  23. M('time2_GS') = 0;
  24. M('time1_EAAT') = 0;
  25. M('time2_EAAT') = 0;
  26. M('alpha_block') = 0;
  27. M('plot') = 0;
  28. M('excite') = 0; % enter a vector of 1x5 of [TSTART TFINAL CURRENT WAVELENGTH PULSEDUTY] to excite the neuron with (CURRENT)pA current starting at TSTART and ending at TEND with wavelength WAVELENGTH and duty DUTY. Values are saved as "excite 1" upto "excite 5"
  31. %% Universal constants
  32. M('F') = 96485.333; % C/mol %Faraday's constant
  33. M('R') = 8314.4598; % (C mV)/(mol K)%Universal gas constant
  34. M('T') = 310; % K %Absolute temperature
  35. M('Zna') = 1; % valence Na
  36. M('Zk') = 1; % valence K
  37. M('ZB') = 1; % valence
  38. M('ZCa') = 2; % valence Ca
  39. M('ZGlu') = -1; % valence Glu
  40. M('Zcl') = -1; % valence Cl
  41. M('ZA') = -1; % valence
  42. M('C') = 20; % pF %membrane constant
  43. M('HeOHa') = 2/3; % Proton ratio (ex:in) in neurons (fixed)
  44. M('Lh2o_n') = 2e-14; % m^3/(ms bar) %Effective membrane water permeability
  45. M('Lh2o_a') = 2e-14; % m^3/(ms bar) %Effective membrane water permeability
  47. %% Permeabilities
  49. %Neuronal channels
  50. M('Pt_Na_n') = 800e-6; %mm^3/ms %Maximal transient Na permeability
  51. M('Pl_Na_n') = 2e-6; %mm^3/ms %Leak Na permeability
  52. M('Pd_K_n') = 400e-6; %mm^3/ms %Maximal delayed rectifier K permeability
  53. M('Pl_K_n') = 2e-5; %mm^3/ms %Leak k permeability
  54. M('Pg_Cl_n') = 19.5e-6; %mm^3/ms %Maximal voltage-gated Cl permeability
  55. M('Pl_Cl_n') = 2.5e-6; %mm^3/ms %Leak Cl permeability
  56. M('Pg_Ca_n') = 1.6e-5; %mm^3/ms %gated Ca permeability
  57. M('Pl_Ca_n') = 4e-10; %mm^3/ms %Leak Ca permeability
  58. M('Pl_Glu_n') = 1e-7; %mm^3/ms %Leak Glu permeability
  60. %Astrocytic channels
  61. M('Pl_Ca_a') = 4e-11; %mm^3/ms %Leak Ca permeability
  62. M('Pl_Glu_a') = 1e-10; %mm^3/ms %Leak Glu permeability
  63. M('Pl_Na_a') = 10e-7;
  64. M('Pl_K_a') = 12e-5;
  65. M('Pl_Cl_a') = 2e-6;
  66. M('Pt_Na_a') = 0.01;
  68. M('g_KDR')=3566.4;
  69. M('P_KDR')=50;
  71. %% Transporters
  73. %KCC transporter
  74. M('Ukcc') = 1.3e-6; % f mol/(ms mV) %KCL cotransporter strength
  76. % %NKA pump from Manu
  77. M('NKA_na') = 13.0; % Half saturation concentration for intracellular Na+
  78. M('NKA_k') = 0.2; % Half saturation concentration for extracellular K+
  79. M('P_NKA') = 110; % Baseline NKA pump strength
  80. M('P_NKA_a') = 90;
  82. %Glutamate recycling
  83. M('k1max') = 1.4e-4; % Glu recycling: Max forward reaction rate
  84. M('KM') = 0.0023; % Glu recycling: Ca half-saturation concentration
  85. M('KDV') = 0.1; % Glu recycling: Half saturation for forward reaction rate
  86. M('k20') = 0.021*1e-3; % Glu recycling: Uncatalysed forward reaction rate
  87. M('k2cat') = 20*1e-3; % Glu recycling: Catalysed forward reaction rate
  88. M('kmin20') = 0.017*1e-3; % Glu recycling: Uncatalysed backward reaction rate
  89. M('kmin1') = 0.05*1e-3; % Glu recycling: Backward reaction rate
  90. M('k3') = 4.4; % Glu recycling: Forward reaction rate
  91. M('kmin3') = 0.001; % Glu recycling: Backward reaction rate
  92. M('k4') = 1.45; % Glu recycling: Fusion rate
  93. M('trec') = 50; % Glu recycling: Vesicle fusion factor
  95. %EAAT neuron
  96. M('alpha_EAAT_n') = 0.0032; % Glutamate transport fitting parameter
  97. M('beta_EAAT_n') = 0.0288; % Glutamate transport fitting parameter
  98. M('rg') = 5e-4;
  99. M('sg') = 9e-2;
  101. %EAAT astrocyte
  102. M('alpha_EAAT_a') = 0.0032; % Glutamate transport fitting parameter
  103. M('beta_EAAT_a') = 0.0288; % Glutamate transport fitting parameter
  104. M('P_EAAT_a') = 120; % EAAT conductance
  106. %NCX
  107. M('P_NCX_n') = 35; % NCX: conductance (1/15 of NKA strength)
  108. M('alphaNaNCX') = 87.5; % NCX: Na half saturation concentration
  109. M('alphaCaNCX') = 1.38; % NCX: Ca half saturation concentration
  110. M('eNCX') = 0.35; % NCX: position of energy barrier
  111. M('ksatNCX') = 0.1; % NCX: saturation factor
  112. M('INCXi0') = -1.4959e-05; % Copied from Manu's computation
  114. %oxygen dynamics parameters
  115. M('alpha_O2') = 5.3/32; % Conversion factor, no unit
  116. M('eps_O2') = 25e-6; % Oxygen diffusion rate, unit: 1/ms
  117. M('O2_e0') = 30;
  118. M('O2_bath') = 40;
  119. M('O2_bath_OD') = 40; % Lower oxygen bath during oxygen deprivation
  121. %Transporters
  122. M('P_Kir') = 0.1;
  123. M('KCe_thres') = 13;
  124. M('P_NKCC1_a') = 100e-7;
  125. M('P_NCX_a') = 1; % NCX conductance
  127. %% Glutamate-Glutamine cycle
  129. %Glutaminase
  130. M('phi_GM') = 1e-7;
  131. M('Km_GM_Gln') = 0.6; % Reference: Kvamme, JNR, 2001
  132. %Glutamine synthetase
  133. M('phi_GS') = 0.3e-6;
  134. M('Km_GS_Glu') = 2.5;
  135. M('Km_GS_NH4') = 0.2;
  136. M('Km_GS_ATP') = 2.3;
  137. M('NH4_a') = 0.15;
  138. %SN transporter
  139. M('Km_SN_Gln') = 1.57;
  140. M('Km_SN_Na') = 31;
  141. M('Km_SN_H') = 100e-6;
  142. M('phi_SN') = 6e-5;
  143. M('P_SN') = 1.755e-4; % fmol/100 mu m^2 ms
  144. M('H_a') = 6.3096e-5;
  145. M('H_e') = 6.3069e-5;
  146. %SAT glutamine transporter
  147. M('Km_SAT_Gln') = 0.3;
  148. M('Km_SAT_Na') = 10;
  149. M('phi_SAT') = 0.00017;
  153. %% Unitial volumes, areas
  154. M('VolPreSyn_n') = 1e-3; % 1000 mu m^3 Presynaptic terminal volume (fixed)
  155. M('VolCleft') = 1e-3; % 1000 mu m^3 Cleft volume (fixed)
  156. M('VolPreSyn_a') = 1e-3;
  157. M('RadiusPreSyn_n') = (M('VolPreSyn_n')*3/4/pi)^(1/3);
  158. M('RadiusPreSyn_a') = (M('VolPreSyn_a')*3/4/pi)^(1/3);
  159. M('AreaPreSyn_n') = 4*pi*M('RadiusPreSyn_n')^2;
  160. M('AreaPreSyn_a') = 4*pi*M('RadiusPreSyn_a')^2;
  162. %% Total molar amounts
  163. %Total sodium, potassium, chloride and volume
  164. M('Tot_N_Na') = 180;
  165. M('Tot_N_K') = 478;
  166. M('Tot_N_Cl') = 1.841874545811657e+02;
  167. M('Tot_Vol') = 4.625000000000000;
  169. %Total calcium,glutamate in the system
  170. M('N_Ca_tot') = 0.001000183047559;
  171. M('N_Gln_tot') = 0.007800000000000;
  172. M('N_Glu_tot') = 0.007010408693616;
  174. M('N_B_a') = 82.485416968700662;
  175. M('N_O2_e0') = 27.750000000000000;
  176. M('N_A_e') = 45;
  177. M('N_A_n') = 2.966822780028186e+02;
  178. M('N_A_a') = 210;
  180. M('P_EAAT_n')=M('P_EAAT_a')/9;
  182. %%
  183. if length(varargin)>1
  184. for i=1:2:length(varargin) % Assign input values to parameters
  185. M(varargin{i}); % If you get an error, one of the labels is misspelled.
  186. if length(varargin{i+1})>1
  187. M(varargin{i})= 1; %the specific key is turned on
  188. for j=1:length(varargin{i+1})
  189. key = join([varargin{i}, j],'_');
  190. M(key)= varargin{i+1}(j); %The different parts of value are saved under 'key 1', 'key 2', ..., 'key n'
  191. end
  192. else
  193. M(varargin{i})= varargin{i+1}; % Assign new values (varargin{i+1}) to labels varargin{i}
  194. end
  195. end
  197. end

Dictionary.m at commit 37d2787, no license · at the source

Overview

Authors: Hannah van Susteren1, Christine R Rose2, Michel J A M van Putten3,4, Hil G E Meijer1
ORCID iDs: Hannah van Susteren, Christine R Rose, Michel J A M van Putten, Hil G E Meijer
  1. Department of Applied Mathematics, University of Twente, Enschede, the Netherlands
  2. Institute of Neurobiology, Heinrich Heine University, Düsseldorf, Germany
  3. Clinical Neurophysiology Group, Department of Science and Technology, University of Twente, Enschede, the Netherlands
  4. Medisch Spectrum Twente, Enschede, the Netherlands
Institutions: University of Twente (Netherlands); Heinrich Heine University Düsseldorf (Germany)
Journal: The European journal of neuroscience, volume 64, issue 1, article e70604
Dates: received 10 November 2025; accepted 12 June 2026; published online 10 July 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1111/ejn.70604 · PMID 42427222 · PMCID PMC13351822 · OpenAlex W4416186287
Open access: hybrid, a free copy (OpenAlex)
Preprint: doi:10.1101/2025.11.10.687543
Status: code verified
Categories: computational modeling (no new data) (modality), human (organism), stroke (population), cellular / molecular (subfield)
Keywords: cerebral ischemia, computational model, glutamate, glutamine, neurotransmitter, synaptic transmission
MeSH: Brain Ischemia*, Glutamic Acid*, Glutamine*, Models, Neurological*, Synaptic Transmission*, Animals, Astrocytes, Humans, Neurons (* major topic)
Topic: Neuroscience and Neuropharmacology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Deutsche Forschungsgemeinschaft (DFG) (Ro2327/14-2, Ro2327/13-2)
Citations: cited by 1 paper (Europe PMC); 67 references in the paper

Abstract

Cerebral ischemia impairs neuronal and glial function, ranging from transient synaptic failure to irreversible damage. The effects of ischemia on excitatory synaptic transmission remain incompletely understood. Here, we present a detailed biophysical model, including the first full implementation of the glutamate–glutamine cycle (GG‐cycle), which is essential for proper functioning of glutamatergic synapses. We model a presynaptic neuron and an astrocyte in a finite extracellular space (ECS), surrounded by an oxygen bath as a proxy for energy supply. The model includes ionic currents with corresponding channels and transporters such as the sodium‐potassium ATPase. To model synaptic transmission, we combine calcium‐dependent glutamate release, its uptake by the sodium‐dependent excitatory amino acid transporters (EAATs), and the GG‐cycle, including glutamine synthesis. We simulate ischemia by blocking energy supply completely. This drives the neuron into depolarization block, with pathological ion concentrations and extracellular glutamate accumulation despite disrupted synaptic release. Synaptic transmission failure is not primarily caused by excessive glutamate release or by failure of glutamine synthetase, but mainly results from EAAT dysfunction, driven by the collapse of the sodium gradient. Restoring synaptic transmission is not possible by solely targeting glutamate dynamics but is possible by restoring ion gradients by inhibition of the voltage‐gated Na+‐channel. Our study highlights the critical role of ion homeostasis, in particular the sodium gradient, in failure and recovery of synaptic function and the EAAT during metabolic stress.

Reproduced under the paper's license (CC BY), from the paper cited above.

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HannahvanSusteren3/GGsyntrans

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 37d2787612916a1ee16bcabff10586d08bed1aec, 6 November 2025
Languages: MATLAB (6)
Size: 13 files, 6 scripts
Software Heritage: not archived
Found in: “Data Availability Statement”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
7 files
At the source: github.com/HannahvanSusteren3/GGsyntrans

The paper's code and data availability statement is in the Data section.

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Data

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Data Availability Statement

The code for all the simulations performed is available at https://github.com/HannahvanSusteren3/GGsyntrans.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 2, 28 September 2026

  • Publisher: n/a → Wiley

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 6 keywords, 9 MeSH terms, 1 funder, 64 references.

Cite

This paper

van Susteren, H., Rose, C. R., van Putten, M. J. A. M., & Meijer, H. G. E. (2026). The Role of the Glutamate-Glutamine Cycle in Synaptic Transmission During Ischemia and Recovery. The European journal of neuroscience, 64(1), e70604. https://doi.org/10.1111/ejn.70604

BibTeX

@article{vansusteren2026role,
author = {van Susteren, Hannah and Rose, Christine R and van Putten, Michel J A M and Meijer, Hil G E},
title = {{The Role of the Glutamate-Glutamine Cycle in Synaptic Transmission During Ischemia and Recovery}},
journal = {The European journal of neuroscience},
year = {2026},
month = jul,
volume = {64},
number = {1},
pages = {e70604},
publisher = {Wiley},
issn = {0953-816X},
doi = {10.1111/ejn.70604},
url = {https://doi.org/10.1111/ejn.70604},
pmid = {42427222},
pmcid = {PMC13351822}
}

RIS

TY - JOUR
AU - van Susteren, Hannah
AU - Rose, Christine R
AU - van Putten, Michel J A M
AU - Meijer, Hil G E
TI - The Role of the Glutamate-Glutamine Cycle in Synaptic Transmission During Ischemia and Recovery
T2 - The European journal of neuroscience
J2 - Eur J Neurosci
PY - 2026
DA - 2026/07/01
VL - 64
IS - 1
SP - e70604
SN - 0953-816X
PB - Wiley
DO - 10.1111/ejn.70604
UR - https://doi.org/10.1111/ejn.70604
LA - en
ER -

CSL-JSON

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"id": "10.1111/ejn.70604",
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"container-title-short": "Eur J Neurosci",
"volume": "64",
"issue": "1",
"page": "e70604",
"DOI": "10.1111/ejn.70604",
"PMID": "42427222",
"PMCID": "PMC13351822",
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"date-parts": [
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