The receptor subunits generating NMDA receptor mediated currents in oligodendrocytes: Oligodendrocyte NMDA responses
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NMDA receptors have been shown to contribute to glutamate-evoked currents in oligodendrocytes. Activation of these receptors damages myelin in ischaemia, in part because they are more weakly blocked by Mg(2+) than are most neuronal NMDA receptors. This weak Mg(2+) block was suggested to reflect an unusual subunit composition including the NR2C and NR3A subunits. Here we expressed NR1/NR2C and triplet NR1/NR2C/NR3A recombinant receptors in HEK cells and compared their currents with those of NMDA-evoked currents in rat cerebellar oligodendrocytes. NR1/NR2C/3A receptors were less blocked by 2 mM Mg(2+) than were NR1/NR2C receptors (the remaining current was 30% and 18%, respectively, of that seen without added Mg(2+)) and showed less channel noise, suggesting a smaller single channel conductance. NMDA-evoked currents in oligodendrocytes showed a Mg(2+) block (to 32%) similar to that observed for NR1/NR2C/NR3A and significantly different from that for NR1/NR2C receptors. Co-immunoprecipitation revealed interactions between NR1, NR2C and NR3A subunits in a purified myelin preparation from rat brain. These data are consistent with NMDA-evoked currents in oligodendrocytes reflecting the activation of receptors containing NR1, NR2C and NR3A subunits.
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In myelin, NR1 is associated with NR2C and NR3A subunits that provide a weak Mg2+ block, suggesting calcium entry does not require prior membrane depolarization.
“In myelin, NR1 is associated with NR2C and NR3A subunits that provide a weak Mg2+ block”
From Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism (2016) · cites this paper as Burzomato et al., 2010
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Arrazola, R., Monteros, A. E. D. L., Serafín, N., Harmony, T., & Quirarte, G. L. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.03.024 · Cited by 1 · see citing works
Metabolic Injury of Oligodendrocytes and Myelin
Stys, P. K. (2012) · doi:10.1093/med/9780199794591.003.0052 · Cited by 1 · see citing works
Regulation of Oligodendrocyte differentiation through Neuroligin-Neurexin signalling
Scott, L. O. M. (2013) · Libraries and Cultural Resources (University of Calgary) · doi:10.11575/prism/27587 · Cited by 1 · see citing works
Sub-clinical glutamate receptor antagonist combinations prevent progressive demyelinationPreprint
Mitchener, V. F. T., Bulman, C., Mellor, A., Bhatt, N., Alghamdi, B. S. A., Nash, J., Proctor, R., Smith, N., Newman, A., Nwabiakam, V., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.19.585708 · Cited by 1 · see citing works
Molecular Architecture and Function Mechanism of Tri-heteromeric GluN1-N2-N3A NMDA ReceptorsPreprint
Kou, Z., Yao, F., Zhang, T., Song, N., Xie, C., Wang, B. M., & Sun, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.25.672209 · Cited by 1 · see citing works
Molecular Architecture and Function Mechanism of Tri-heteromeric GluN1-N2-N3A NMDA ReceptorsPreprint
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Molecular Architecture and Function Mechanism of Tri-heteromeric GluN1-N2-N3A NMDA ReceptorsPreprint
Kou, Z., Yao, F., Zhang, T., Song, N., Xie, C., Wang, B. M., & Sun, Y. (2025) · eLife · doi:10.7554/elife.108752 · Cited by 1 · see citing works
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Physiology of Oligodendrocytes
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Molecular impact of anti-NMDA receptor autoantibodies
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Electrical responses of oligodendrocytes to pathological stimuli
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- Authors
- Burzomato, V., Frugier, G., Pérez-Otaño, I., Kittler, J. T., & Attwell, D.
- Affiliations
- University College London (GB)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2010-09-15
- Volume
- 588
- Issue
- 18
- Pages
- 3403-3414
- ISSN
- 0022-3751 (ISSN-L)
- PMC
- PMC2988507
- OpenAlex
- W1503609844
- Cited by
- 78
- References
- 36
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 8 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 2 · 2013: 12 · 2012: 8
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- 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, oligodendrocytes, receptor subunit composition, NR1 subunit, Mg2+ block, myelin damage, ischemia, channel noise, single-channel conductance, subunit interactions, myelin
- MeSH terms
- Animals, Cerebellum, Evoked Potentials, Gene Expression Regulation, Humans, Magnesium, Oligodendroglia, Receptors, N-Methyl-D-Aspartate, Protein Isoforms, Protein Subunits, Rats, Electrophysiological Phenomena, HEK293 Cells
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