The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Identification and Mechanism of Action of Two Histidine Residues Underlying High-Affinity Zn2+ Inhibition of the NMDA Receptor
Open accessAbstract
Zinc (Zn2+) inhibition of N-methyl-D-aspartate receptor (NMDAR) activity involves both voltage-independent and voltage-dependent components. Recombinant NR1/NR2A and NR1/NR2B receptors exhibit similar voltage-dependent block, but voltage-independent Zn2+ inhibition occurs with much higher affinity for NR1/NR2A than NR1/NR2B receptors (nanomolar versus micromolar IC50, respectively). Here, we show that two neighboring histidine residues on NR2A represent the critical determinant (termed the "short spacer") for high-affinity, voltage-independent Zn2+ inhibition using the Xenopus oocyte expression system and site-directed mutagenesis. Mutation of either one of these two histidine residues (H42 and H44) in the extracellular N-terminal domain of NR2A shifted the IC50 for high-affinity Zn2+ inhibition approximately 200-fold without affecting the EC50 of the coagonists NMDA and glycine. We suggest that the mechanism of high-affinity Zn2+ inhibition on the NMDAR involves enhancement of proton inhibition.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“Of note, even transient GSH deficits are sufficient to induce NMDAR hypofunction 70 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [70]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The biochemical basis of zinc physiology
Vallée, B. L., & Falchuk, K. H. (1993) · Physiological Reviews · doi:10.1152/physrev.1993.73.1.79 · Cited by 3,005
Heteromeric NMDA receptors: molecular and functional distinction of subtypes
Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B., & Seeburg, P. H. (1992) · Science · doi:10.1126/science.256.5060.1217 · Cited by 2,541
Molecular cloning and characterization of the rat NMDA receptor
Moriyoshi, K., Masu, M., Ishii, T., Shigemoto, R., Mizuno, N., & Nakanishi, S. (1991) · Nature · doi:10.1038/354031a0 · Cited by 1,771
Changing subunit composition of heteromeric NMDA receptors during development of rat cortex
Sheng, M., Cummings, J., Roldan, L. A., Jan, Y. N., & Jan, L. Y. (1994) · Nature · doi:10.1038/368144a0 · Cited by 1,377
Molecular diversity of the NMDA receptor channel
Kutsuwada, T., Kashiwabuchi, N., Mori, H., Sakimura, K., Kushiya, E., Araki, K., Meguro, H., Hisashi, M., Kumanishi, T., Arakawa, M., et al. (1992) · Nature · doi:10.1038/358036a0 · Cited by 1,352
Release of endogenous Zn2+ from brain tissue during activity
Assaf, S. Y., & Chung, S. (1984) · Nature · doi:10.1038/308734a0 · Cited by 1,113
Chemical Modification of Proteins
Roberts, G. C. K. (2012) · Springer eBooks · doi:10.1007/978-3-642-16712-6_100145 · Cited by 1,074
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs
Liman, E. R., Tytgat, J., & Hess, P. (1992) · Neuron · doi:10.1016/0896-6273(92)90239-a · Cited by 1,072
The Role of Zinc in Selective Neuronal Death After Transient Global Cerebral Ischemia
Koh, J., Suh, S. W., Gwag, B. J., He, Y. Y., Hsu, C. Y., & Choi, D. W. (1996) · Science · doi:10.1126/science.272.5264.1013 · Cited by 1,070
Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits.
Ishii, T. M., Moriyoshi, K., Sugihara, H., Sakurada, K., Kadotani, H., Yokoi, M., Akazawa, C., Shigemoto, R., Mizuno, N., & Masu, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53849-7 · Cited by 980
Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons
Westbrook, G. L., & Mayer, M. L. (1987) · Nature · doi:10.1038/328640a0 · Cited by 852
Stimulation-induced uptake and release of zinc in hippocampal slices
Howell, G. A., Welch, M. G., & Frederickson, C. (1984) · Nature · doi:10.1038/308736a0 · Cited by 820
Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs
Meguro, H., Mori, H., Araki, K., Kushiya, E., Kutsuwada, T., Yamazaki, M., Kumanishi, T., Arakawa, M., Sakimura, K., & Mishina, M. (1992) · Nature · doi:10.1038/357070a0 · Cited by 799
Zinc Selectively Blocks the Action of N -Methyl-D-Aspartate on Cortical Neurons
Peters, S., Koh, J., & Choi, D. W. (1987) · Science · doi:10.1126/science.2883728 · Cited by 668
High-Affinity Zinc Inhibition of NMDA NR1–NR2A Receptors
Paoletti, P., Ascher, P., & Neyton, J. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05711.1997 · Cited by 667
Zinc potentiates agonist-lnduced currents at certain splice variants of the NMDA receptor
Hollmann, M., Boulter, J., Maron, C., Beasley, L., Sullivan, J., Pecht, G., & Heinemann, S. F. (1993) · Neuron · doi:10.1016/0896-6273(93)90209-a · Cited by 614
Modulation of pH by neuronal activity
Chesler, M., & Kaila, K. (1992) · Trends in Neurosciences · doi:10.1016/0166-2236(92)90191-a · Cited by 533
Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing
Sugihara, H., Moriyoshi, K., Ishii, T. M., Masu, M., & Nakanishi, S. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91701-q · Cited by 524
Control by Asparagine Residues of Calcium Permeability and Magnesium Blockade in the NMDA Receptor
Burnashev, N., Schoepfer, R., Monyer, H., Ruppersberg, J. P., Gunther, W. C., Seeburg, P. H., & Sakmann, B. J. (1992) · Science · doi:10.1126/science.1382314 · Cited by 455
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc
Smart, T. G., Xie, X., & Krishek, B. J. (1994) · Progress in Neurobiology · doi:10.1016/0301-0082(94)90082-5 · Cited by 443
Hollmann, M., Maron, C., & Heinemann, S. (1994) · Neuron · doi:10.1016/0896-6273(94)90419-7 · Cited by 421
Control of Proton Sensitivity of the NMDA Receptor by RNA Splicing and Polyamines
Traynelis, S. F., Hartley, M., & Heinemann, S. F. (1995) · Science · doi:10.1126/science.7754371 · Cited by 416
Chemical Modification of Proteins
Wood, E. (1974) · Biochemical Education · doi:10.1016/0307-4412(74)90019-3 · Cited by 404
Luo, J., Wang, Y., Yasuda, R. P., Dunah, A. W., & Wolfe, B. B. (1997) · Molecular Pharmacology · doi:10.1124/mol.51.1.79 · Cited by 399
A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission
Xie, X., & Smart, T. G. (1991) · Nature · doi:10.1038/349521a0 · Cited by 378
Durand, G. M., Gregor, P., Zheng, X., Bennett, M. V. L., Uhl, G. R., & Zukin, R. S. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9359 · Cited by 308
Effect of zinc on NMDA receptor-mediated channel currents in cortical neurons
Christine, C. W., & Choi, D. W. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-01-00108.1990 · Cited by 301
Mayer, M. L., Vyklický, L., & Westbrook, G. (1989) · The Journal of Physiology · doi:10.1113/jphysiol.1989.sp017724 · Cited by 272
Control of Voltage-Independent Zinc Inhibition of NMDA Receptors by the NR1 Subunit
Traynelis, S. F., Burgess, M. F., Zheng, F., Lyuboslavsky, P. N., & Powers, J. L. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-16-06163.1998 · Cited by 268
Identification by mutagenesis of a Mg2+ -block site of the NMDA receptor channel
Mori, H., Hisashi, M., Yamakura, T., & Mishina, M. (1992) · Nature · doi:10.1038/358673a0 · Cited by 262
Sullivan, J. M., Traynelis, S. F., Chen, H.-S. V., Escobar, W. A., Heinemann, S. F., & Lipton, S. A. (1994) · Neuron · doi:10.1016/0896-6273(94)90258-5 · Cited by 249
Self-citationDifferential Sensitivity of RecombinantN-Methyl-d-Aspartate Receptor Subtypes to Zinc Inhibition
Chen, N., Moshaver, A., & Raymond, L. A. (1997) · Molecular Pharmacology · doi:10.1124/mol.51.6.1015 · Cited by 221
Neuroprotective Effects of Glutamate Antagonists and Extracellular Acidity
Kaku, D. A., Giffard, R. G., & Choi, D. W. (1993) · Science · doi:10.1126/science.8389056 · Cited by 202
Holmgren, M., Shin, K. S., & Yellen, G. (1998) · Neuron · doi:10.1016/s0896-6273(00)80571-1 · Cited by 198
Transmembrane topology of two kainate receptor subunits revealed by N-glycosylation.
Wo, Z. G., & Oswald, R. E. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.15.7154 · Cited by 195
Preferential co-assembly of recombinant NMDA receptors composed of three different subunits
Wafford, K. A., Bain, C., Bourdellès, B. L., Whiting, P. J., & Kemp, J. A. (1993) · Neuroreport · doi:10.1097/00001756-199309150-00015 · Cited by 190
Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition
Zheng, F., Gingrich, M. B., Traynelis, S. F., & Conn, P. J. (1998) · Nature Neuroscience · doi:10.1038/634 · Cited by 182
Legendre, P., & Westbrook, G. L. (1990) · The Journal of Physiology · doi:10.1113/jphysiol.1990.sp018266 · Cited by 171
Structural conservation of ion conduction pathways in K channels and glutamate receptors.
Wood, M. W., VanDongen, H. M. A., & VanDongen, A. M. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4882 · Cited by 161
Sakurada, K., Masu, M., & Nakanishi, S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54166-1 · Cited by 155
Zinc alters excitatory amino acid neurotoxicity on cortical neurons
Koh, J., & Choi, D. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-06-02164.1988 · Cited by 136
Leonard, J. P., & Kelso, S. R. (1990) · Neuron · doi:10.1016/0896-6273(90)90443-j · Cited by 124
Separating dual effects of zinc at recombinant N-methyl-d-aspartate receptors
Williams, K. L. (1996) · Neuroscience Letters · doi:10.1016/s0304-3940(96)12924-4 · Cited by 111
Fisher, J. L., & Macdonald, R. L. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02944.1998 · Cited by 102
A single histidine residue is essential for zinc inhibition of GABA rho 1 receptors
Wang, T., Hackam, A. S., Guggino, W. B., & Cutting, G. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-11-07684.1995 · Cited by 83
Horenstein, J., & Akabas, M. H. (1998) · PubMed · Cited by 82
Wooltorton, J. R. A., McDonald, B. J., Moss, S. J., & Smart, T. G. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.633ba.x · Cited by 75
Cited by
Sorted by citations
Glutamate receptor ion channels
Mayer, M. L. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.004 · Cited by 3,655
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568
Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging
Que, E. L., Domaille, D. W., & Chang, C. J. (2008) · Chemical Reviews · doi:10.1021/cr078203u · Cited by 2,077
NMDA receptor subunits: function and pharmacology
PAOLETTI, P., & NEYTON, J. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.08.011 · Cited by 887
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686
Metadata
- Authors
- Choi, Y.-B., & Lipton, S. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Lipton, Stuart A
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 23
- Issue
- 1
- Pages
- 171-180
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1970564284
- Cited by
- 180
- References
- 48
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 5 · 2014: 10 · 2013: 4 · 2012: 12
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R01EY005477)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD029587)
- 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 › Receptor Mechanisms and Signaling
- Keywords
- zinc inhibition, NMDA receptor, NR2A subunit, histidine residues, voltage-dependent block, proton inhibition, site-directed mutagenesis
- MeSH terms
- Animals, Diethyl Pyrocarbonate, Female, Histidine, Mutation, Oocytes, Xenopus laevis, Zinc, Receptors, N-Methyl-D-Aspartate, Patch-Clamp Techniques, Protein Isoforms
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