Glutamate Induces Calcium Waves in Cultured Astrocytes: Long-Range Glial Signaling
Abstract
The finding that astrocytes possess glutamate-sensitive ion channels hinted at a previously unrecognized signaling role for these cells. Now it is reported that cultured hippocampal astrocytes can respond to glutamate with a prompt and oscillatory elevation of cytoplasmic free calcium, visible through use of the fluorescent calcium indicator fluo-3. Two types of glutamate receptor—one preferring quisqualate and releasing calcium from intracellular stores and the other preferring kainate and promoting surface-membrane calcium influx—appear to be involved. Moreover, glutamate-induced increases in cytoplasmic free calcium frequently propagate as waves within the cytoplasm of individual astrocytes and between adjacent astrocytes in confluent cultures. These propagating waves of calcium suggest that networks of astrocytes may constitute a long-range signaling system within the brain.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Astrocytes reside in close proximity to neuronal synapses and express glutamate receptors that regulate Ca2+ influx to influence ATP signaling.
“Astrocytes reside in close proximity to neuronal synapses and express glutamate receptors that regulate CA 2+ influx (Cornell-Bell et al, 1990) to influence ATP signaling (Cotrina et al, 2000).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Cornell-Bell et al, 1990
Cites
Inositol phosphates and cell signalling
Berridge, M. J., & Irvine, R. F. (1989) · Nature · doi:10.1038/341197a0 · Cited by 4,061 · see citing works
Specification of Cerebral Cortical Areas
Rakic, P. (1988) · Science · doi:10.1126/science.3291116 · Cited by 3,127 · see citing works
Quinoxalinediones: Potent Competitive Non-NMDA Glutamate Receptor Antagonists
Honoré, T., Davies, S. N., Drejer, J., Fletcher, E. J., Jacobsen, P., Lodge, D., & Nielsen, F. (1988) · Science · doi:10.1126/science.2899909 · Cited by 1,191 · see citing works
Photochemically generated cytosolic calcium pulses and their detection by fluo-3
Kao, J. P. Y., Harootunian, A. T., & Tsien, R. Y. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83166-0 · Cited by 818 · see citing works
Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes
Woods, N. M., Cuthbertson, K., & Cobbold, P. H. (1986) · Nature · doi:10.1038/319600a0 · Cited by 793 · see citing works
A new type of glutamate receptor linked to inositol phospholipid metabolism
Sugiyama, H., Ito, I., & Hirono, C. (1987) · Nature · doi:10.1038/325531a0 · Cited by 760 · see citing works
Raff, M., Abney, E., Cohen, J., Lindsay, R., & Noble, M. (1983) · The Journal of Neuroscience · doi:10.1523/jneurosci.03-06-01289.1983 · Cited by 759 · see citing works
Sáez, J. C., Connor, J. A., Spray, D. C., & Bennett, M. V. L. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.8.2708 · Cited by 595 · see citing works
Regulation of calcium influx by second messengers in rat mast cells
Penner, R., Matthews, G., & Neher, E. (1988) · Nature · doi:10.1038/334499a0 · Cited by 494 · see citing works
Repetitive spikes in cytoplasmic calcium evoked by histamine in human endothelial cells
Jacob, R., Merritt, J. E., Hallam, T. J., & RINK, T. J. (1988) · Nature · doi:10.1038/335040a0 · Cited by 408 · see citing works
Excitatory amino acids directly depolarize rat brain astrocytes in primary culture
Bowman, C. L., & Kimelberg, H. K. (1984) · Nature · doi:10.1038/311656a0 · Cited by 357 · see citing works
Voltage-Dependent Calcium Channels in Glial Cells
MacVicar, B. A. (1984) · Science · doi:10.1126/science.6095454 · Cited by 344 · see citing works
Multiple conductance channels in type-2 cerebellar astrocytes activated by excitatory amino acids
Usowicz, M. M., Gallo, V., & Cull-Candy, S. G. (1989) · Nature · doi:10.1038/339380a0 · Cited by 276 · see citing works
A new mechanism for glutamate receptor action: phosphoinositide hydrolysis
Sladeczek, F. A. J., Récasens, M., & Bockaert, J. (1988) · Trends in Neurosciences · doi:10.1016/0166-2236(88)90183-x · Cited by 240 · see citing works
Kettenmann, H., & Schachner, M. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-12-03295.1985 · Cited by 217 · see citing works
Barres, B. A., Chun, L. L. Y., & Corey, D. P. (1989) · Neuron · doi:10.1016/0896-6273(89)90076-7 · Cited by 190 · see citing works
Astrocyte glutamate receptor activation promotes inositol phospholipid turnover and calcium flux
Pearce, B., Albrecht, J., Morrow, C., et al. (1986) · Neuroscience Letters · doi:10.1016/0304-3940(86)90537-9 · Cited by 187 · see citing works
Schoepp, D. D., & Johnson, B. G. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb03050.x · Cited by 179 · see citing works
Forscher, P., Kaczmarek, L. K., Buchanan, J., et al. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-11-03600.1987 · Cited by 177 · see citing works
Jensen, A., & Chiu, S. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-04-01165.1990 · Cited by 175 · see citing works
Barres, B., Chun, L., & Corey, D. P. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-09-03169.1989 · Cited by 173 · see citing works
The Ca2+/Cl− dependent L‐[3H]glutamate binding: a new receptor or a particular transport process?
Pin, J., Bockaert, J., & Recasesn, M. (1984) · FEBS Letters · doi:10.1016/0014-5793(84)80563-3 · Cited by 171 · see citing works
Sugiyama, H., Ito, I., & Watanabe, M. (1989) · Neuron · doi:10.1016/0896-6273(89)90121-9 · Cited by 163 · see citing works
Plasma membrane contacts in the central nervous system.
Peters, A. (1962) · PubMed · Cited by 125 · see citing works
Quantitative physiological characterization of a quinoxalinedione non- NMDA receptor antagonist
Yamada, K. A., Dubinsky, J., & Rothman, S. M. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-09-03230.1989 · Cited by 94 · see citing works
Calcium oscillations in non-excitable cells
RINK, T. J., & Jacob, R. (1989) · Trends in Neurosciences · doi:10.1016/0166-2236(89)90133-1 · Cited by 94 · see citing works
Opening of dihydropyridine calcium channels in skeletal muscle membranes by inositol trisphosphate
Vilven, J., & Coronado, R. (1988) · Nature · doi:10.1038/336587a0 · Cited by 80 · see citing works
Applications of quantitative measurements for assessing glutamate neurotoxicity.
Finkbeiner, S. M., & Stevens, C. F. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.11.4071 · Cited by 80 · see citing works
Self-citationFacilitation of voltage-gated ion channels in frog neuroglia by nerve impulses
Marrero, H. G., Astion, M. L., Coles, J. A., et al. (1989) · Nature · doi:10.1038/339378a0 · Cited by 71 · see citing works
The Neuronal Microenvironment: A Comparative View
Cserr, H. F., & Bundgaard, M. (1986) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1986.tb27134.x · Cited by 50 · see citing works
Membrane conductance oscillations in astrocytes induced by phorbol ester
MacVicar, B. A., Crichton, S. A., Burnard, D. M., et al. (1987) · Nature · doi:10.1038/329242a0 · Cited by 44 · see citing works
Gräf, P., Dahl, S. V., & Sies, H. (1987) · Biochemical Journal · doi:10.1042/bj2410933 · Cited by 40 · see citing works
Intercellular signaling as visualized by endogenous calcium-dependent bioluminescence
Brehm, P., Lechleiter, J. D., Smith, S. J., et al. (1989) · Neuron · doi:10.1016/0896-6273(89)90032-9 · Cited by 37 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595 · see citing works
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196 · see citing works
Tripartite synapses: glia, the unacknowledged partner
Araque, A., Parpura, V., Sanzgiri, R. P., & Haydon, P. G. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01349-6 · Cited by 2,529 · see citing works
Tripartite synapses: astrocytes process and control synaptic information
Perea, G., Navarrete, M., & Araque, A. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.001 · Cited by 1,820 · see citing works
Diversity of astrocyte functions and phenotypes in neural circuits
Khakh, B. S., & Sofroniew, M. V. (2015) · Nature Neuroscience · doi:10.1038/nn.4043 · Cited by 1,239 · see citing works
Astrocytic Purinergic Signaling Coordinates Synaptic Networks
Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J.-Y., Takano, H., Moss, S. J., McCarthy, K., & Haydon, P. G. (2005) · Science · doi:10.1126/science.1116916 · Cited by 1,280 · see citing works
Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934 · see citing works
The tripartite synapse: roles for gliotransmission in health and disease
Halassa, M. M., Fellin, T., & Haydon, P. G. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.12.005 · Cited by 852 · see citing works
Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo
Nimmerjahn, A., Kirchhoff, F., Kerr, J. N. D., & Helmchen, F. (2004) · Nature Methods · doi:10.1038/nmeth706 · Cited by 784 · see citing works
Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice
Kuchibhotla, K. V., Lattarulo, C. R., Hyman, B. T., & Bacskai, B. J. (2009) · Science · doi:10.1126/science.1169096 · Cited by 729 · see citing works
Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo
Wang, X., Lou, N., Xu, Q., Tian, G.-F., Peng, W. G., Han, X., Kang, J., Takano, T., & Nedergaard, M. (2006) · Nature Neuroscience · doi:10.1038/nn1703 · Cited by 685 · see citing works
Yuste, R., & Katz, L. C. (1991) · Neuron · doi:10.1016/0896-6273(91)90243-s · Cited by 591 · see citing works
Signaling at the Gliovascular Interface
Simard, M., Arcuino, G., Takano, T., Liu, Q. S., & Nedergaard, M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-27-09254.2003 · Cited by 586 · see citing works
The neurovascular unit - concept review
Muoio, V., Persson, P. B., & Sendeski, M. M. (2014) · Acta Physiologica · doi:10.1111/apha.12250 · Cited by 564 · see citing works
The Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516 · see citing works
Activity-dependent structural and functional plasticity of astrocyte-neuron interactions
Theodosis, D. T., Poulain, D. A., & Oliet, S. H. R. (2008) · Physiological Reviews · doi:10.1152/physrev.00036.2007 · Cited by 531 · see citing works
Neuronal Domains in Developing Neocortex
Yuste, R., Peinado, A., & Katz, L. C. (1992) · Science · doi:10.1126/science.1496379 · Cited by 490 · see citing works
Brain lactate metabolism: the discoveries and the controversies
Dienel, G. A. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.175 · Cited by 479 · see citing works
Beyond the role of glutamate as a neurotransmitter
Nedergaard, M., Takano, T., & Hansen, A. J. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn916 · Cited by 450 · see citing works
Role of Astrocytes in Neurovascular Coupling
Petzold, G. C., & Murthy, V. N. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.009 · Cited by 409 · see citing works
The role of astroglia in neuroprotection
Bélanger, M., & Magistretti, P. J. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.3/mbelanger · Cited by 396 · see citing works
Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion
Verkhratsky, A., Matteoli, M., Parpura, V., Mothet, J., & Zorec, R. (2016) · The EMBO Journal · doi:10.15252/embj.201592705 · Cited by 397 · see citing works
Cotrina, M. L., Lin, J. H.-C., López-Garcı́a, J. C., Naus, C. C. G., & Nedergaard, M. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-08-02835.2000 · Cited by 388 · see citing works
Iwata, M., Ota, K. T., Li, X.-Y., Sakaue, F., Li, N., Dutheil, S., Banasr, M., Duric, V., Yamanashi, T., Kaneko, K., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.11.026 · Cited by 387 · see citing works
Astrocyte regulation of synaptic behavior
Allen, N. J. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-013053 · Cited by 343 · see citing works
Garaschuk, O., Hanse, E., & Konnerth, A. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.219bu.x · Cited by 348 · see citing works
Gliotransmission: Beyond Black-and-White
Savtchouk, I., & Volterra, A. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.0017-17.2017 · Cited by 325 · see citing works
Control of glial immune function by neurons
Neumann, H. (2001) · Glia · doi:10.1002/glia.1108 · Cited by 319 · see citing works
Araque, A., Martı́n, E. D., Perea, G., Arellano, J. I., & Buño, W. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-07-02443.2002 · Cited by 283 · see citing works
Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal
Weber, M. D., Godbout, J. P., & Sheridan, J. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.102 · Cited by 283 · see citing works
Molecular signals of plasticity at the tetrapartite synapse
Dityatev, A., & Rusakov, D. A. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.12.006 · Cited by 267 · see citing works
An astroglial basis of major depressive disorder? An overview
Wang, Q., Jie, W., Liu, J., Yang, J., & Gao, T. (2017) · Glia · doi:10.1002/glia.23143 · Cited by 222 · see citing works
Tchieu, J., Calder, E. L., Guttikonda, S. R., Gutzwiller, E. M., Aromolaran, K. A., Steinbeck, J. A., Goldstein, P. A., & Studer, L. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0035-0 · Cited by 231 · see citing works
Yamamoto, T., Ochalski, A., Hertzberg, E. L., & Nagy, J. I. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.903020414 · Cited by 230 · see citing works
Cerebral Hemodynamics and Vascular Risk Factors: Setting the Stage for Alzheimer's Disease
de la Torre, J. C. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-120793 · Cited by 219 · see citing works
A global view of protein expression in human cells, tissues, and organs
Pontén, F., Gry, M., Fagerberg, L., Lundberg, E., Asplund, A., Berglund, L., Oksvold, P., Björling, E., Hober, S., Kampf, C., et al. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.93 · Cited by 222 · see citing works
Gq-DREADD Selectively Initiates Glial Glutamate Release and Inhibits Cue-induced Cocaine Seeking
Scofield, M. D., Boger, H. A., Smith, R. J., Li, H., Haydon, P. G., & Kalivas, P. W. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.02.016 · Cited by 197 · see citing works
Do stars govern our actions? Astrocyte involvement in rodent behavior
Oliveira, J. F., Sardinha, V. M., Guerra-Gomes, S., Araque, A., & Sousa, N. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.07.006 · Cited by 189 · see citing works
Di Benedetto, G., Burgaletto, C., Bellanca, C. M., Munafò, A., Bernardini, R., & Cantarella, G. (2022) · Cells · doi:10.3390/cells11172728 · Cited by 189 · see citing works
Retinal Macroglial Responses in Health and Disease
de Hoz, R., Rojas, B., Ramírez, A. I., Salazar, J. J., Gallego, B. I., Triviño, A., & Ramírez, J. M. (2016) · BioMed Research International · doi:10.1155/2016/2954721 · Cited by 187 · see citing works
Danesh-Meyer, H. V., Kerr, N. M., Zhang, J., Eady, E. K., O'Carroll, S. J., Nicholson, L. F. B., Johnson, C. S., & Green, C. R. (2012) · Brain · doi:10.1093/brain/awr338 · Cited by 179 · see citing works
Calcium signaling and gliotransmission in normal vs. reactive astrocytes
Agulhon, C., Sun, M.-Y., Murphy, T., Myers, T., Lauderdale, K., & Fiacco, T. A. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00139 · Cited by 167 · see citing works
Glutamate‐mediated neuronal–glial transmission
Verkhratsky, A., & Kirchhoff, F. (2007) · Journal of Anatomy · doi:10.1111/j.1469-7580.2007.00734.x · Cited by 156 · see citing works
Astrocytic contributions to bioenergetics of cerebral ischemia
Dienel, G. A., & Hertz, L. (2005) · Glia · doi:10.1002/glia.20157 · Cited by 150 · see citing works
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126 · see citing works
Dermietzel, R. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00031-3 · Cited by 117 · see citing works
Avila-Muñoz, E., & Arias, C. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.07.004 · Cited by 114 · see citing works
Purinergic signalling and intercellular Ca2+ wave propagation in the organ of Corti
Piazza, V., Ciubotaru, C. D., Gale, J. E., & Mammano, F. (2007) · Cell Calcium · doi:10.1016/j.ceca.2006.05.005 · Cited by 105 · see citing works
Calcium-induced release of calcium in muscle: 50 years of work and the emerging consensus
Ríos, E. (2018) · Journal of General Physiology · doi:10.1085/jgp.201711959 · Cited by 103 · see citing works
GABA release from astrocytes in health and disease.
Kilb, W., & Kirischuk, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415859 · Cited by 66 · see citing works
Astroglial Calcium Signalling in Alzheimer's Disease
Verkhratsky, A., Rodríguez-Arellano, J. J., Parpura, V., & Zorec, R. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.088 · Cited by 55 · see citing works
Intercellular Ca<sup>2+</sup> signalling in the adult mouse cochlea
Sirko, P., Gale, J. E., & Ashmore, J. F. (2019) · The Journal of Physiology · doi:10.1113/jp276400 · Cited by 34 · see citing works
- Authors
- Cornell-Bell, A. H., Finkbeiner, S. M., Cooper, M. S., & Smith, S. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Science
- Published
- 1990-01-26
- Volume
- 247
- Issue
- 4941
- Pages
- 470-473
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2090971379
- Cited by
- 1,846
- References
- 33
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 37 · 2023: 43 · 2022: 30 · 2021: 73 · 2020: 39 · 2019: 55 · 2018: 41 · 2017: 38 · 2016: 65 · 2015: 65 · 2014: 50 · 2013: 52 · 2012: 63
- FWCI
- 30.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01ns016671-07a1, 5r01ns012961-22)
- National Institute of General Medical Sciences (GM07205, T32GM007205)
- National Institute of Neurological Disorders and Stroke (NS16671-09, NS-12961-14)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- glutamate, calcium waves, astrocytes, hippocampal astrocytes, glutamate receptors, kainate receptors, quisqualate receptors, intracellular calcium stores, calcium influx, astrocyte networks
- MeSH terms
- Aniline Compounds, Astrocytes, Calcium, Cells, Cultured, Cytoplasm, Fluorescent Dyes, Glutamates, Hippocampus, Intercellular Junctions, Kainic Acid, Oxadiazoles, Periodicity, Xanthenes, Quisqualic Acid, Receptors, Glutamate, Receptors, Neurotransmitter, Glutamic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
