Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability.
The 3 matches · 1 of them tie a paragraph to a whole file without given lines: a weak match, whose lines are not tinted
- [1] § Modelling › Mathematical Model for Ca2+ Oscillations ↔ model_run.m, lines 6 to 53 · score 0.76 · simplified model, SERCA pumping, ER lumen, clearance, IP3, activation · Report a mismatch
- [2] § Modelling › Model Parameters ↔ model_run.m, lines 6 to 53 · score 0.76 · half max, IP3R, strength, binding, cytoplasmic, WT · Report a mismatch
- [3] § Modelling › Mathematical Model for Ca2+ Oscillations ↔ calcium_ode_cyto_V.m, the whole file · a weak match · score 0.56 · SERCA pumping, IP3 receptors, SOCE, dynamics · Report a mismatch
Paper
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The authors' code
MATLAB · 85 lines · 2.6 KB · no license · 2 matches
- % This script simulates Ca2+ dynamics with hardcoded parameters for two cases:
- % - Wild Type (WT): set volchange = 1 and params.k_soce = 6.5227
- % - RTN3OE: set volchange = 4.3808 and params.k_soce = 3.9583
- % Ensure the matching k_soce value is uncommented when switching between cases
- %% Setup Ca2+ model parameters
- volchange = 1; % Set to 1 to run simulation with the ER volume of WT
- % Volume of ER and cytosol (μm^3)
- params.VER = 212;
- params.Vcyto = 4/3 * pi * (10^3 - 5^3) - params.VER; % Cell minus nucleus minus ER
- % IP3R Ca2+ release rate (μm^3/s)
- params.v1 = 69.075;
- % Passive leak rate (μm^3/s)
- params.v2 = 0.00;
- % SERCA pump rate (μM·μm^3/s)
- params.v3 = 496;
- % Cytoplasmic clearance rate (μM·μm^3/s)
- params.v4 = 368;
- % Half-max [Ca2+] for cytosolic clearance (μM)
- params.k_pl = 0.106;
- % SOCE entry rate (μm^3/s)
- params.k_soce = 6.5227; % for WT
- %params.k_soce = 3.9583; % for RTN3OE
- % Extracellular Ca2+ concentration (μM)
- params.c_cs = 200;
- % Half-max constants for IP3R gating (μM)
- params.k_er = 0.117; % SERCA half-max [Ca2+] (μM)
- params.d_ip3 = 0.1300; % IP3 binding (μM)
- params.d_act = 0.0823; % Activation by Ca2+ (μM)
- % inhibition by Ca, not using the simplified model, different IP3 binding
- % strength depending on whether Ca is present in other sites
- d2 = 1.049; d3 = 0.9434;
- params.d_inh = d2*(params.IP3 + params.d_ip3)/(params.IP3 + d3); % μM
- params.a = 0.5940; % h-gate kinetics (1/μM/s)
- % IP3 concentration (μM)
- params.IP3 = 0.4;
- % Buffer parameters in ER lumen
- params.k_D = 201.6; % Dissociation constant (μM)
- params.S = 2700 / volchange; % Total buffer site conc. (μM)
- params0 = params; % Save a copy
- %% Initial conditions
- c_cyto0 = 0.06; % Initial cytosolic free Ca2+ (μM)
- h0 = 0.8; % Initial h-inactivation variable
- u_er0 = 170; % Initial ER free Ca2+ (μM)
- c_er0 = u_er0 + u_er0 * params.S / (u_er0 + params.k_D); % Total ER Ca2+ (free + bound)
- % Initial state vector: [cytosol Ca2+, h, ER free Ca2+, ER total Ca2+]
- y0 = [c_cyto0; h0; u_er0; c_er0];
- % Time span (s)
- tspan = [0, 480];
- % Solve ODE system
- [t, y] = ode45(@(t, y) calcium_ode_cyto_V(t, y, params), tspan, y0);
- %% Plot cytosolic and ER free Ca2+ over time
- subplot(2,1,1);
- plot(t/60, y(:,1), 'LineWidth', 2);
- plot_cleanup(gca, 'FontSize', 16)
- ylabel('$c_\mathrm{cyto}\;\; \mu M$');
- xlabel('Time (min)');
- title('Cytosol Ca$^{2+}$');
- legend off
- subplot(2,1,2);
- plot(t/60, y(:,3), 'LineWidth', 2);
- plot_cleanup(gca, 'FontSize', 16)
- ylabel('$u_\mathrm{ER}\;\; \mu M$');
- xlabel('Time (min)');
- title('ER free Ca$^{2+}$');
- legend off
model_run.m at commit f577f4e, no license · at the source
Overview
- Department of Clinical Neurosciences UK Dementia Research Institute at University of Cambridge Cambridge UK
- Department of Physics University of California San Diego, La Jolla California USA
- GIMM – Gulbenkian Institute for Molecular Medicine Avenida Prof. Egas Moniz Lisboa Portugal
- Faculdade de Medicina Universidade De Lisboa Av. Prof. Egas Moniz Lisboa Portugal
- Mitochondrial Neurobiology Laboratory The Francis Crick Institute London UK
- Department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology and Neuroscience King's College London London UK
- Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK
- Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology University College London London UK
- Cambridge Institute for Medical Research (CIMR) Department of Medicine University of Cambridge Cambridge UK
Abstract
The endoplasmic reticulum (ER)’s continuous morphology is tightly controlled by ER‐shaping proteins, whose genetic or expression defects drive a spectrum of neurodegenerative disorders from Hereditary Spastic Paraplegia to Alzheimer's disease. Why perturbations in ER morphology manifest specifically in neurons remains unknown. Here, by coupling visualisation of global sub‐Hz firing bursts to ER ultrastructural manipulations in human inducible Pluripotent Stem Cells (hiPSC)‐derived cortical neurons, alongside physical simulations, we establish a key ER structure‐function principle: neuronal ER architecture dictates Ca2+ replenishment speed. Altering ER structure hinders network ER luminal connectivity and Ca2+ propagation from refill points at plasma membrane contact sites, impairing the ER's capability to supply repetitive Ca2+ bursts. The ER morpho‐regulatory control of Ca2+ refill speed thus constitutes a switch on neuronal activity. Further, perturbed ER shape also abolishes Ca2+ firing and contraction in primary skeletal muscle cells. These results expose the selective vulnerability of Ca2+‐firing cells to ER structural disruptions, rationalizing ER dysfunction in neurodegeneration and unveiling a new role for the continuous ER morphology that could apply universally to Ca2+‐firing cells.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repositories
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lenafabr/networkSpreadFVM
7a33595ded23d64e9ec2ef41c439528dae422c98, 22 January 2026Availability: 2 checks, the latest on 31 October 2026: the link answers
- 31 October 2026: the link answers
- 30 September 2026: the link answers
49 files
- scripts/
MeshObj.m , MATLAB, 123 lines - scripts/
Mixed_sys.m , MATLAB, 43 lines - scripts/
circle_reservoir_mesh.m , MATLAB, 235 lines - scripts/
circlenuchex_sheets.m , MATLAB, 453 lines - scripts/
circlenuchex_sheets_mess , MATLAB, 459 linesy.m - scripts/
example1_ca.m , MATLAB, 90 lines - scripts/
example_PA.m , MATLAB, 42 lines - scripts/
interpolateMeshPos.m , MATLAB, 23 lines - scripts/
loadSnapshotFVM.m , MATLAB, 62 lines - scripts/
loadTotFluxSim.m , MATLAB, 28 lines - scripts/
makenetwork_circlenuchex , MATLAB, 237 linesmesh.m - scripts/
meshPatches.m , MATLAB, 79 lines - scripts/
perm_diff.m , MATLAB, 97 lines - scripts/
perm_plot.m , MATLAB, 69 lines - scripts/
ploter.m , MATLAB, 119 lines - scripts/
polygon_reservoir_mesh.m , MATLAB, 246 lines - scripts/
pploter.m , MATLAB, 193 lines - scripts/
segcircintersect.m , MATLAB, 34 lines - scripts/
testCone20240523.m , MATLAB, 103 lines - scripts/
testglobalresv20240429.m , MATLAB, 69 lines - scripts/
testglobalresv20240501.m , MATLAB, 133 lines - scripts/
testreleaseLin20240521.m , MATLAB, 155 lines - scripts/
testspreadWT20240501.m , MATLAB, 110 lines - scripts/
testspreadlin20240501.m , MATLAB, 112 lines - scripts/
work20220419.m , MATLAB, 26 lines - scripts/
work20230824.m , MATLAB, 120 lines - scripts/
work20230908.m , MATLAB, 148 lines - source/
dynsysutil.f90 , Fortran, 982 lines - source/
flowutil.f90 , Fortran, 128 lines - source/
fvmdynamics.f90 , Fortran, 899 lines - source/
keys.f90 , Fortran, 194 lines - source/
main.f90 , Fortran, 201 lines - source/
meshutil.f90 , Fortran, 1,303 lines - source/
networkutil.f90 , Fortran, 960 lines - source/
nodecontractutil.f90 , Fortran, 231 lines - source/
readkey.f90 , Fortran, 925 lines - source/
resvutil.f90 , Fortran, 262 lines - source/
test.f90 , Fortran, 39 lines - source/
testmain.f90 , Fortran, 141 lines - source/
tools/ , Fortran, 2,006 linesdgmres.f90 - source/
tools/ , Fortran, 409 linesgenutil.f90 - source/
tools/ , Fortran, 584 linesgmresutil.f90 - source/
tools/ , Fortran, 361 linesinputparams.f90 - source/
tools/ , Fortran, 322 linesmt19937.f90 - source/
tools/ , Fortran, 6,056 linesslatec.f90 - source/
tools/ , Fortran, 2,006 lineszgmres.f90 - tmp.f90, Fortran, 1 line
- LICENSE, License, 674 lines
- README.md, Text, 33 lines
lenafabr/aspatialCaERrefill
f577f4e0f280742c4c111cffdb0f76c622e352bc, 11 July 2025Availability: 2 checks, the latest on 31 October 2026: the link answers
- 31 October 2026: the link answers
- 30 September 2026: the link answers
3 files
- calcium_ode_cyto_V.m, MATLAB, 45 lines, 1 match
- model_run.m, MATLAB, 85 lines, 2 matches
- README.md, Text, 10 lines
Tracing map
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Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 7 keywords, 6 MeSH terms, 5 funders, 68 references, 6 RRIDs.
Cite
This paper
Davi, V., Parutto, P., Zhang, Y., Konno, T., Crapart, C., Pereira, R., Franklin, J. P., Awadelkareem, M. A., Maddison, D. C., Devine, M. J., Gomes, E. R., Chambers, J., Koslover, E., & Avezov, E. (2026). Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(36), e21101. https://
BibTeX
@article{davi2026endopla
author = {Davi, Valentina and Parutto, Pierre and Zhang, Yuyi and Konno, Tasuku and Crapart, Cecile and Pereira, Raquel and Franklin, John P. and Awadelkareem, Mosab Ali and Maddison, Daniel C and Devine, Michael J. and Gomes, Edgar R. and Chambers, Joseph and Koslover, Elena and Avezov, Edward},
title = {{Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = mar,
volume = {13},
number = {36},
pages = {e21101},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/
url = {https://
pmid = {41915835},
pmcid = {PMC13317608}
}
RIS
TY - JOUR
AU - Davi, Valentina
AU - Parutto, Pierre
AU - Zhang, Yuyi
AU - Konno, Tasuku
AU - Crapart, Cecile
AU - Pereira, Raquel
AU - Franklin, John P.
AU - Awadelkareem, Mosab Ali
AU - Maddison, Daniel C
AU - Devine, Michael J.
AU - Gomes, Edgar R.
AU - Chambers, Joseph
AU - Koslover, Elena
AU - Avezov, Edward
TI - Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/
VL - 13
IS - 36
SP - e21101
SN - 2198-3844
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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