Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons
Abstract
1. We examined whether synaptically activated N-methyl-D-aspartate (NMDA) receptors are regulated by intracellular calcium in cultured hippocampal neurons by comparing excitatory postsynaptic currents (EPSCs) to the previously described calcium-dependent regulation of whole cell NMDA currents. Standard whole cell recording and fast application methods were used. 2. Low-frequency (0.2 Hz) stimulation of EPSCs in the presence of 2-amino-5-phosphonovalerate (AP5) evoked a constant amplitude alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSC. On removal of AP5 in Ca(2+)-containing solutions, the amplitude of the slow NMDA receptor-mediated EPSC decreased by approximately 50% during the next 10 stimuli. The decrease in the EPSC was dependent on the extracellular calcium concentration and stimulus frequency, consistent with Ca(2+)-dependent desensitization/inactivation of postsynaptic NMDA receptors. A whole cell prepulse of NMDA (10 microM, 10 s) in Ca(2+)-containing solutions inhibited the slow EPSC to a similar degree. A series of slow EPSCs also produced Ca(2+)-dependent inactivation of whole cell NMDA currents evoked in low calcium solutions. 3. These results demonstrate that synaptic NMDA receptors are inactivated by intracellular calcium and that calcium entry through synaptically activated NMDA receptors is sufficient to provide feedback inhibition of the slow EPSC.
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The initiation of phase 2 would involve the desensitization or rundown of NMDA receptors, which occurs in response to a dramatic increase in postsynaptic calcium concentration.
“The initiation of phase 2 would involve the desensitization (Zorumski and Thio [265]; Rosenmund et al. [266]; Swope et al. [267]; Nakamichi and Yoneda [268]) or rundown (Rosenmund and Westbrook [269]; Alford et al. [270]; Price et al. [271]) of NMDA receptors, which occurs in response to a dramatic increase in postsynaptic calcium concentation.”
From The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes-Dodson Law (2007) · cites this paper as Rosenmund et al. [266]
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- Authors
- Rosenmund, C., Feltz, A., & Westbrook, G. L.
- Affiliations
- Oregon Health & Science University (US)
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 1995-01-01
- Volume
- 73
- Issue
- 1
- Pages
- 427-430
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W1944475919
- Cited by
- 166
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 6
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH-46613)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- NMDA receptor, hippocampal neurons, excitatory postsynaptic currents, calcium influx, product inhibition, AMPA receptors, stimulus frequency dependence
- MeSH terms
- Animals, Calcium, Evoked Potentials, Hippocampus, Synaptic Transmission, Neurons, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Rats, Sprague-Dawley, 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 ›
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