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Functional Ca2+-permeable AMPA receptors in hippocampal astrocytes mediate calcium signaling in vitro
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  • Published: 05 April 2026

Functional Ca2+-permeable AMPA receptors in hippocampal astrocytes mediate calcium signaling in vitro

  • Javier Picañol1,2,
  • Aida Castellanos1,7,
  • Esther Gratacòs-Batlle3,
  • Roberto García1,4,
  • Silvia Ginés5,6,7,
  • Xavier Gasull1,7,
  • Lydia Jiménez-Díaz8,
  • Juan D. Navarro-López8 &
  • …
  • David Soto1,7 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cell biology
  • Neuroscience
  • Physiology

Abstract

Glutamate is the main excitatory neurotransmitter in the brain, acting through ionotropic receptors such as AMPA receptors (AMPARs). While their neuronal role is well established, AMPAR function in astrocytes remains poorly understood, especially in the hippocampus. In this study, we investigated the expression and functional properties of astrocytic AMPARs, focusing on their capacity to mediate calcium signaling and inter-cellular communication. Using astrocyte primary cultures, we confirmed the expression of GluA1 and GluA2 subunits, along with detectable levels of GluA4. Calcium imaging revealed that pharmacological AMPAR stimulation elicited intracellular Ca²⁺ signals in a subset of astrocytes which were markedly potentiated when desensitization was impaired. Notably, some of these responses persisted without extracellular Na⁺, compatible with the presence of functional calcium-permeable AMPARs (CP-AMPARs) in hippocampal astrocytes. However, sodium was required for full amplification of the Ca²⁺ signals, suggesting a synergistic role of Na⁺ and Ca²⁺ influx. Pharmacological inhibition of GluA2-lacking AMPARs reduced the responses, supporting the coexistence of GluA2-lacking and GluA2-containing subtypes. Sniffer-calcium assays suggested that strong AMPAR stimulation can engage ATP-dependent signaling, facilitating calcium wave propagation. Altogether, our results reveal functional and heterogeneous AMPAR populations in hippocampal astrocytes. Further investigations will elucidate their physiological roles, localization, and contribution to neuroglial interactions under physiological and pathological conditions.

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AMPAR:

AMPA receptor

CP-AMPAR:

Calcium-permeable AMPA receptor

CI-AMPAR:

Calcium-impermeable AMPA receptor

CTZ:

Cyclothiazide

DIV:

Days in vitro

DMEM:

Dulbecco’s Modified Eagle Medium

FBS:

Fetal Bovine Serum

GFAP:

Glial fibrillary acidic protein

GLAST:

Glutamate aspartate transporter

GFP:

Green fluorescent protein

GRIA:

Glutamate receptor, ionotropic, AMPA

HBSS:

Hank’s Balanced Salt Solution

IP3R:

Inositol-1,4,5-triphosphate receptor

LTP:

Long-term potentiation

LTD:

Long-term depression

NASPM:

1-Naphthyl acetyl spermine

NBQX:

2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline

PAM:

Positive allosteric modulator

PBS:

Phosphate-buffered saline

PBS-CM:

PBS with Calcium and Magnesium

SEM:

Standard error of the mean

TARP:

Transmembrane AMPA receptor regulatory protein

TBS-T:

Tris-buffered saline with Tween-20

References

  1. Hansen, K. B. et al. Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels. Pharmacol. Rev. 73, 298–487 (2021).

    Google Scholar 

  2. Fonnum, F. Glutamate: a neurotransmitter in mammalian brain. J. Neurochem. 42, 1–11 (1984).

    Google Scholar 

  3. Huganir, R. L. & Nicoll, R. A. AMPARs and synaptic plasticity: the last 25 years. Neuron 80, 704–717 (2013).

    Google Scholar 

  4. Nabavi, S. et al. Engineering a memory with LTD and LTP. Nature 511, 348–352 (2014).

    Google Scholar 

  5. Miguez-Cabello, F. et al. AMPAR/TARP stoichiometry differentially modulates channel properties. Elife 9, e53946 (2020).

    Google Scholar 

  6. Schwenk, J. et al. Regional diversity and developmental dynamics of the AMPA-receptor proteome in the mammalian brain. Neuron 84, 41–54 (2014).

    Google Scholar 

  7. Lu, W. et al. Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Neuron 62, 254–268 (2009).

    Google Scholar 

  8. Bats, C., Farrant, M. & Cull-Candy, S. G. A role of TARPs in the expression and plasticity of calcium-permeable AMPARs: Evidence from cerebellar neurons and glia. Neuropharmacology 74, 76–85 (2013).

    Google Scholar 

  9. Cull-Candy, S. G. & Farrant, M. Ca2+ -permeable AMPA receptors and their auxiliary subunits in synaptic plasticity and disease. J. Physiol. 599, 2655–2671 (2021).

    Google Scholar 

  10. Burnashev, N., Monyer, H., Seeburg, P. H. & Sakmann, B. Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8, 189–198 (1992).

    Google Scholar 

  11. Higuchi, M. et al. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406, 78–81 (2000).

    Google Scholar 

  12. Swanson, G. T., Kamboj, S. K. & Cull-Candy, S. G. Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. J. Neurosci. 17, 58–69 (1997).

    Google Scholar 

  13. Bowie, D. & Mayer, M. L. Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron 15, 453–462 (1995).

    Google Scholar 

  14. Greger, I. H., Khatri, L. & Ziff, E. B. RNA Editing at Arg607 Controls AMPA Receptor Exit from the Endoplasmic Reticulum. Neuron 34, 759–772 (2002).

    Google Scholar 

  15. Greger, I. H., Khatri, L., Kong, X. & Ziff, E. B. AMPA Receptor Tetramerization Is Mediated by Q/R Editing. Neuron 40, 763–774 (2003).

    Google Scholar 

  16. Park, P. et al. On the Role of Calcium-Permeable AMPARs in Long-Term Potentiation and Synaptic Tagging in the Rodent Hippocampus. Front. Synaptic Neurosci. 11, 4 (2019).

    Google Scholar 

  17. Iino, M. et al. Glia-Synapse Interaction Through Ca2+-Permeable AMPA Receptors in Bergmann Glia. Science 292, 926–929 (2001).

    Google Scholar 

  18. Noda, M., Nakanishi, H., Nabekura, J. & Akaike, N. AMPA–Kainate Subtypes of Glutamate Receptor in Rat Cerebral Microglia. J. Neurosci. 20, 251–258 (2000).

    Google Scholar 

  19. Bergles, D. E., Roberts, J. D. B., Somogyi, P. & Jahr, C. E. Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187–191 (2000).

    Google Scholar 

  20. Mölders, A., Koch, A. & Menke, R. Klöcker, N. Heterogeneity of the astrocytic AMPA-receptor transcriptome. Glia 66, 2604–2616 (2018).

    Google Scholar 

  21. Batiuk, M. Y. et al. Identification of region-specific astrocyte subtypes at single cell resolution. Nat. Commun. 11, 1220 (2020).

    Google Scholar 

  22. Ceprian, M. & Fulton, D. Glial Cell AMPA Receptors in Nervous System Health, Injury and Disease. Int. J. Mol. Sci. 20, 2450 (2019).

    Google Scholar 

  23. Zhou, M. & Kimelberg, H. K. Freshly isolated hippocampal CA1 astrocytes comprise two populations differing in glutamate transporter and AMPA receptor expression. J. Neurosci. 21, 7901–7908 (2001).

    Google Scholar 

  24. Fan, D. et al. AMPA receptor protein expression and function in astrocytes cultured from hippocampus. J. Neurosci. Res. 57, 557–571 (1999).

    Google Scholar 

  25. Lalo, U., Pankratov, Y., Kirchhoff, F., North, R. A. & Verkhratsky, A. NMDA receptors mediate neuron-to-glia signaling in mouse cortical astrocytes. J. Neurosci. 26, 2673–2683 (2006).

    Google Scholar 

  26. Droste, D. et al. Ca2+-permeable AMPA receptors in mouse olfactory bulb astrocytes. Sci. Rep. 7, 44817 (2017).

    Google Scholar 

  27. Blakemore, L. J., Resasco, M., Mercado, M. A. & Trombley, P. Q. Evidence for Ca(2+)-permeable AMPA receptors in the olfactory bulb. Am. J. Physiol. Cell. Physiol. 290, C925–935 (2006).

    Google Scholar 

  28. Burnashev, N. et al. Calcium-Permeable AMPA-Kainate Receptors in Fusiform Cerebellar Glial Cells. Science 256, 1566–1570 (1992).

    Google Scholar 

  29. Scrutton, A. M. et al. Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum. Science https://doi.org/10.1126/science.aeb3577 (2025). eaeb3577.

    Google Scholar 

  30. Douyard, J., Shen, L., Huganir, R. L. & Rubio, M. E. Differential neuronal and glial expression of GluR1 AMPA receptor subunit and the scaffolding proteins SAP97 and 4.1 N during rat cerebellar development. J. Comp. Neurol. 502, 141–156 (2007).

    Google Scholar 

  31. Matsui, K., Jahr, C. E. & Rubio, M. E. High-Concentration Rapid Transients of Glutamate Mediate Neural-Glial Communication via Ectopic Release. J. Neurosci. 25, 7538–7547 (2005).

    Google Scholar 

  32. Soto, D. et al. Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5. Nat. Neurosci. 12, 277–285 (2009).

    Google Scholar 

  33. Saab, A. S. et al. Bergmann glial AMPA receptors are required for fine motor coordination. Science 337, 749–753 (2012).

    Google Scholar 

  34. Skowrońska, K., Obara-Michlewska, M., Zielińska, M. & Albrecht, J. NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis. Int. J. Mol. Sci. 20, 309 (2019).

    Google Scholar 

  35. Perea, G., Navarrete, M. & Araque, A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 32, 421–431 (2009).

    Google Scholar 

  36. Leybaert, L. & Sanderson, M. J. Intercellular Ca(2+) waves: mechanisms and function. Physiol. Rev. 92, 1359–1392 (2012).

    Google Scholar 

  37. Bazargani, N. & Attwell, D. Astrocyte calcium signaling: the third wave. Nat. Neurosci. 19, 182–189 (2016).

    Google Scholar 

  38. Petzold, G. C. & Murthy, V. N. Role of astrocytes in neurovascular coupling. Neuron 71, 782–797 (2011).

    Google Scholar 

  39. Goenaga, J., Araque, A. & Kofuji, P. Herrera Moro Chao, D. Calcium signaling in astrocytes and gliotransmitter release. Front. Synaptic Neurosci. 15, 1138577 (2023).

    Google Scholar 

  40. Wang, X. et al. Astrocytic Ca2 + signaling evoked by sensory stimulation in vivo. Nat. Neurosci. 9, 816–823 (2006).

    Google Scholar 

  41. Takano, T. et al. Astrocyte-mediated control of cerebral blood flow. Nat. Neurosci. 9, 260–267 (2006).

    Google Scholar 

  42. Cahoy, J. D. et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278 (2008).

    Google Scholar 

  43. Sun, W. et al. Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science 339, 197–200 (2013).

    Google Scholar 

  44. Srinivasan, R. et al. Ca(2+) signaling in astrocytes from Ip3r2(-/-) mice in brain slices and during startle responses in vivo. Nat. Neurosci. 18, 708–717 (2015).

    Google Scholar 

  45. Güler, B. E., Krzysko, J. & Wolfrum, U. Isolation and culturing of primary mouse astrocytes for the analysis of focal adhesion dynamics. STAR. Protoc. 2, 100954 (2021).

    Google Scholar 

  46. Nolte, C. et al. GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue. Glia 33, 72–86 (2001).

    Google Scholar 

  47. Lovatt, D. et al. The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J. Neurosci. 27, 12255–12266 (2007).

    Google Scholar 

  48. Partin, K. M., Patneau, D. K. & Mayer, M. L. Cyclothiazide differentially modulates desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor splice variants. Mol. Pharmacol. 46, 129–138 (1994).

    Google Scholar 

  49. Sun, Y. et al. Mechanism of glutamate receptor desensitization. Nature 417, 245–253 (2002).

    Google Scholar 

  50. Sheardown, M. J., Nielsen, E. O., Hansen, A. J., Jacobsen, P. & Honoré, T. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. Science 247, 571–574 (1990).

    Google Scholar 

  51. Geiger, J. R. et al. Relative abundance of subunit mRNAs determines gating and Ca2 + permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron 15, 193–204 (1995).

    Google Scholar 

  52. Miguez-Cabello, F. et al. GluA2-containing AMPA receptors form a continuum of Ca2+-permeable channels. Nature 641, 537–544 (2025).

    Google Scholar 

  53. Kirischuk, S., Héja, L., Kardos, J. & Billups, B. Astrocyte sodium signaling and the regulation of neurotransmission. Glia 64, 1655–1666 (2016).

    Google Scholar 

  54. Koike, M., Iino, M. & Ozawa, S. Blocking effect of 1-naphthyl acetyl spermine on Ca2+-permeable AMPA receptors in cultured rat hippocampal neurons. Neurosci. Res. 29, 27–36 (1997).

    Google Scholar 

  55. Allen, T. G. J. The `sniffer-patch’ technique for detection of neurotransmitter release. Trends Neurosci. 20, 192–197 (1997).

    Google Scholar 

  56. Suadicani, S. O., Brosnan, C. F. & Scemes, E. P2X7 Receptors Mediate ATP Release and Amplification of Astrocytic Intercellular Ca2 + Signaling. J. Neurosci. 26, 1378–1385 (2006).

    Google Scholar 

  57. Fumagalli, M. et al. Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors. Glia 43, 218–203 (2003).

    Google Scholar 

  58. Egan, T. M. & Khakh, B. S. Contribution of Calcium Ions to P2X Channel Responses. J. Neurosci. 24, 3413–3420 (2004).

    Google Scholar 

  59. Volterra, A., Liaudet, N. & Savtchouk, I. Astrocyte Ca2+ signalling: an unexpected complexity. Nat. Rev. Neurosci. 15, 327–335 (2014).

    Google Scholar 

  60. Queiroz, G., Meyer, D. K., Meyer, A. & Starke, K. Kügelgen, I. A study of the mechanism of the release of ATP from rat cortical astroglial cells evoked by activation of glutamate receptors. Neuroscience 91, 1171–1181 (1999). von.

    Google Scholar 

  61. Ahmadpour, N. et al. Cortical astrocyte N-methyl-D-aspartate receptors influence whisker barrel activity and sensory discrimination in mice. Nat. Commun. 15, 1571 (2024).

    Google Scholar 

  62. Höft, S., Griemsmann, S., Seifert, G. & Steinhäuser, C. Heterogeneity in expression of functional ionotropic glutamate and GABA receptors in astrocytes across brain regions: insights from the thalamus. Philos. Trans. R Soc. Lond. B Biol. Sci. 369, 20130602 (2014).

    Google Scholar 

  63. David, J. C., Yamada, K. A., Bagwe, M. R. & Goldberg M. P. AMPA receptor activation is rapidly toxic to cortical astrocytes when desensitization is blocked. J. Neurosci. 16, 200–209 (1996).

    Google Scholar 

  64. Rose, C. R. & Verkhratsky, A. Glial ionic excitability: The role for sodium. Glia 64, 1609–1610 (2016).

    Google Scholar 

  65. Langer, J. & Rose, C. R. Synaptically induced sodium signals in hippocampal astrocytes in situ. J. Physiol. 587, 5859–5877 (2009).

    Google Scholar 

  66. Rose, C. R., Ziemens, D. & Verkhratsky, A. On the special role of NCX in astrocytes: Translating Na+-transients into intracellular Ca2 + signals. Cell. Calcium. 86, 102154 (2020).

    Google Scholar 

  67. Rysted, J. E. et al. Distinct properties of Ca2 + efflux from brain, heart and liver mitochondria: The effects of Na+, Li + and the mitochondrial Na+/Ca2 + exchange inhibitor CGP37157. Cell. Calcium. 96, 102382 (2021).

    Google Scholar 

  68. Podestà, A. et al. The polyamine naphthyl-acetyl spermine trihydrochloride (NASPM) lacks specificity for Ca2+-permeable AMPA receptors and suppresses seizure like activity in human brain tissue by inhibition of NMDA receptors. Preprint at https://doi.org/10.1101/2025.05.14.653650 (2025).

  69. Pascual, O. et al. Astrocytic purinergic signaling coordinates synaptic networks. Science 310, 113–116 (2005).

    Google Scholar 

  70. Pangršič, T. et al. Exocytotic release of ATP from cultured astrocytes. J. Biol. Chem. 282, 28749–28758 (2007).

    Google Scholar 

  71. Kang, J. et al. Connexin 43 Hemichannels Are Permeable to ATP. J. Neurosci. 28, 4702–4711 (2008).

    Google Scholar 

  72. Fujii, Y., Maekawa, S. & Morita, M. Astrocyte calcium waves propagate proximally by gap junction and distally by extracellular diffusion of ATP released from volume-regulated anion channels. Sci. Rep. 7, 13115 (2017).

    Google Scholar 

  73. Lines, J., Corkrum, M., Aguilar, J. & Araque, A. The Duality of Astrocyte Neuromodulation: Astrocytes Sense Neuromodulators and Are Neuromodulators. J. Neurochem. 169, e70054 (2025).

    Google Scholar 

  74. Burnstock, G. Physiopathological Roles of P2X Receptors in the Central Nervous System. CMC 22, 819–844 (2015).

    Google Scholar 

  75. Kato, A. S. et al. Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins. Neuron 68, 1082–1096 (2010).

    Google Scholar 

  76. Carbone, A. L. & Plested, A. J. R. Superactivation of AMPA receptors by auxiliary proteins. Nat. Commun. 7, 10178 (2016).

    Google Scholar 

  77. Carrillo, E. et al. Mechanism of modulation of AMPA receptors by TARP-γ8. J. Gen. Physiol. 152 (e201912451), jgp201912451 (2020).

    Google Scholar 

  78. Tomita, S. et al. Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins. J. Cell. Biol. 161, 805–816 (2003).

    Google Scholar 

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Acknowledgements

We would like to sincerely thank Dr. Mercè Izquierdo for her invaluable support and guidance with the calcium imaging analysis. We are also grateful to Ms. Alba Pereda and Dr. Nadia Di Franco from the Histology Unit of the Institute of Neurosciences at the University of Barcelona for their assistance. We thank the Scientific and Technological Centers (CCiTUB), Universitat de Barcelona, and staff members Gemma Martin and Maria Calvo for their support and advice on fluorescence microscopy techniques. This work was supported by Grant PID2020-119932GB-I00 to D.S and PID2024-155505OB-I00 funded by MICIU/AEI/10.13039/501100011033 (MINECO) to D.S. and E.G.B; Grants PID2020-119305RB-I00 and PID2023-148439OB-I00 funded by MCIN/AEI/10.13039/501100011033 (MINECO) to X.G.; 2021SGR00292 from the Generalitat de Catalunya (to D.S. and X.G.); María de Maeztu Unit of Excellence CEX2021-001159-M, supported by MCIN/AEI/10.13039/501100011033, to the Institut de Neurociències, Universitat de Barcelona; PID2020–115823-GBI00 (MCIN/AEI/10.13039/501100011033) to L.J.D. and J.D.N.L.; PID2021-123732OB-I00 (MCIN/AEI/10.13039/501100011033) to S.G.; and the Spanish Ministry of Universities FPU fellowship FPU22/02071 to J.P.

Author information

Authors and Affiliations

  1. Neurophysiology Laboratory, Physiology Unit, Department of Biomedicine, Medical School, Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain

    Javier Picañol, Aida Castellanos, Roberto García, Xavier Gasull & David Soto

  2. Department of Health Sciences, TecnoCampus University Center, Pompeu Fabra University, Mataró, Barcelona, Spain

    Javier Picañol

  3. Department of Fundamental and Clinical Nursing, Faculty of Nursing, Institute of Neurosciences, Universitat de Barcelona, L’Hospitalet de Llobregat, Spain

    Esther Gratacòs-Batlle

  4. Facultad de Ingeniería, Programa de Ingeniería Biomédica, Universidad Militar Nueva Granada, kilómetro 2 Cajicá-Zipaquirá, Bogotá, Colombia

    Roberto García

  5. Histology Unit, Department of Biomedicine, Medical School, Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain

    Silvia Ginés

  6. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain

    Silvia Ginés

  7. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Aida Castellanos, Silvia Ginés, Xavier Gasull & David Soto

  8. Neurophysiology & Behavior Lab, School of Medicine of Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain

    Lydia Jiménez-Díaz & Juan D. Navarro-López

Authors
  1. Javier Picañol
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  9. David Soto
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Contributions

J.P. performed most of the experiments including calcium imaging, wester blotting and sniffer assays, analyzed the data, and wrote the initial draft of the manuscript. A.C. contributed to experimental design, performed supporting calcium imaging experiments, assisted in data analysis, figure preparation and original illustrations used to schematize the methodology. E.G.B. performed western blotting and immunofluorescence experiments, provided technical support, contributed to data interpretation, and assisted in manuscript preparation. R.G. contributed to experimental procedures and general laboratory support. S.G. contributed to the design and supervision of molecular biology experiments and provided key resources. X.G. provided scientific resources related to calcium imaging and contributed to the conceptual framework. He supervised aspects of data interpretation and revised the manuscript for intellectual content. L.J.D. and J.D.N.L. supported the project through institutional resources and supervision and offered conceptual input during the whole process. D.S. conceived and led the project, providing intellectual guidance throughout all stages. He secured funding, supervised the experimental design, data analysis, and interpretation, and was responsible for writing and critically revising the final version of the manuscript. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Javier Picañol or David Soto.

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Picañol, J., Castellanos, A., Gratacòs-Batlle, E. et al. Functional Ca2+-permeable AMPA receptors in hippocampal astrocytes mediate calcium signaling in vitro. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41403-8

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  • Received: 11 July 2025

  • Accepted: 19 February 2026

  • Published: 05 April 2026

  • DOI: https://doi.org/10.1038/s41598-026-41403-8

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Keywords

  • glia
  • astrocyte
  • calcium signaling
  • AMPA receptors
  • calcium-permeable AMPARs
  • hippocampus
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