Synaptic Desensitization of NMDA Receptors by Calcineurin
Abstract
Desensitization is a phenomenon that is common to many ligand-gated ion channels but has been demonstrated only rarely with physiological stimulation. Numerous studies describe desensitization of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor by exogenous agonists, but whether synaptic stimulation causes desensitization has been unknown. Synaptic stimulation of NMDA receptors on rat hippocampal neurons resulted in desensitization that was prevented by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), adenosine-5'-O-(3-thiotriphosphate) (ATP-gamma-S), or inhibitors of phosphatase 2B (calcineurin), but not by inhibitors of phosphatases 1 and 2A or of tyrosine phosphatases. Synaptic NMDA receptors may fluctuate between phosphorylated and dephosphorylated forms, depending on the rate of synaptic stimulation and the magnitude of the associated influx of calcium through NMDA receptors.
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?
Both calcineurin and F-actin are involved in controlling the efficacy of NMDA receptors.
“Both calcineurin and F-actin are involved in controlling the efficacy of NMDA receptors (Rosenmund and Westbrook, 1993;Lieberman and Mody, 1994;Tong et al., 1995).”
From Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin (1998) · cites this paper as Tong et al., 1995
Cites
Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons
Rosenmund, C., Feltz, A., & Westbrook, G. L. (1995) · Journal of Neurophysiology · doi:10.1152/jn.1995.73.1.427 · Cited by 166 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068 · see citing works
Spike Timing–Dependent Plasticity: A Hebbian Learning Rule
Caporale, N., & Dan, Y. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.060407.125639 · Cited by 1,997 · see citing works
The principal features and mechanisms of dopamine modulation in the prefrontal cortex
Seamans, J. K., & Yang, C. R. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.05.006 · Cited by 1,592 · see citing works
Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity
Yashiro, K., & Philpot, B. D. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.046 · Cited by 649 · see citing works
Stathopoulos, A. M., & Cyert, M. S. (1997) · Genes & Development · doi:10.1101/gad.11.24.3432 · Cited by 442 · see citing works
Cunningham, K. W., & Fink, G. R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.5.2226 · Cited by 431 · see citing works
Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin
Halpain, S., Hipolito, A., & Saffer, L. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09835.1998 · Cited by 408 · see citing works
“Both calcineurin and F-actin are involved in controlling the efficacy of NMDA receptors (Rosenmund and Westbrook, 1993; Lieberman and Mody, 1994; Tong et al., 1995).”
BackgroundMolecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment
Konradi, C., & Heckers, S. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00328-5 · Cited by 336 · see citing works
The absence of a major Ca <sup>2+</sup> signaling pathway in GABAergic neurons of the hippocampus
Sík, A., Hájos, N., Gulácsi, A., Mody, I., & Freund, T. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.3245 · Cited by 186 · see citing works
Possible involvement of group I mGluRs in neuroprotective effect of theanine
Nagasawa, K., Aoki, H., Yasuda, E., Nagai, K., Shimohama, S., & Fujimoto, S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.143 · Cited by 48 · see citing works
Excitotoxicity Triggered by Neurobasal Culture Medium
Hogins, J., Crawford, D. C., Zorumski, C. F., & Mennerick, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025633 · Cited by 41 · see citing works
Wu, P., Zhao, Y., Haidacher, S. J., Wang, E., Parsley, M. O., Gao, J., Sadygov, R. G., Starkey, J. M., Luxon, B. A., Spratt, H., et al. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2012.2391 · Cited by 36 · see citing works
- Authors
- Tong, G., Shepherd, D., & Jahr, C. E.
- Affiliations
- Oregon Health & Science University (US)
- Venue
- Science
- Published
- 1995-03-10
- Volume
- 267
- Issue
- 5203
- Pages
- 1510-1512
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2079311079
- Cited by
- 404
- References
- 1
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 4 · 2023: 10 · 2022: 6 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 9 · 2017: 8 · 2016: 3 · 2015: 10 · 2014: 13 · 2013: 8 · 2012: 12
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-21419, R01NS021419)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- NMDA receptor desensitization, calcineurin, synaptic stimulation, receptor phosphorylation, dephosphorylation, hippocampal neurons, calcium influx, ATP gamma S, BAPTA, glutamate receptors, synaptic plasticity
- MeSH terms
- Adenosine Triphosphate, Animals, Calcium, Calmodulin-Binding Proteins, Cells, Cultured, Egtazic Acid, Electric Stimulation, Glycine, Hippocampus, Membrane Potentials, Neurons, Phosphoprotein Phosphatases, Phosphorylation, Synapses, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Patch-Clamp Techniques, Calcineurin, Rats
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
