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.
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
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?
Even transient GSH deficits are sufficient to induce NMDAR hypofunction.
“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.
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 · see citing works
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 · see citing works
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 · see citing works
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 1,346 · see citing works
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 1,170 · see citing works
Release of endogenous Zn2+ from brain tissue during activity
Assaf, S. Y., & Chung, S. (1984) · Nature · doi:10.1038/308734a0 · Cited by 1,113 · see citing works
Chemical Modification of Proteins
Roberts, G. C. K. (2012) · Springer eBooks · doi:10.1007/978-3-642-16712-6_100145 · Cited by 1,074 · see citing works
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 · see citing works
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 · see citing works
Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits.
Ishii, T., 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 982 · see citing works
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 · see citing works
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 · see citing works
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 798 · see citing works
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 667 · see citing works
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 650 · see citing works
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 611 · see citing works
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 · see citing works
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 523 · see citing works
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.
Smart, T., Xie, X., & Krishek, B. (1994) · Progress in neurobiology · doi:10.1016/0301-0082(94)90082-5 · Cited by 459 · see citing works
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 447 · see citing works
Luo, J.-H., Wang, Y.-H., Yasuda, R., Dunah, A., & Wolfe, B. (1997) · Molecular Pharmacology · doi:10.1124/mol.51.1.79 · Cited by 427 · see citing works
Hollmann, M., Maron, C., & Heinemann, S. (1994) · Neuron · doi:10.1016/0896-6273(94)90419-7 · Cited by 417 · see citing works
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 411 · see citing works
Chemical Modification of Proteins
Wood, E. (1974) · Biochemical Education · doi:10.1016/0307-4412(74)90019-3 · Cited by 404 · see citing works
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 · see citing works
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 309 · see citing works
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 299 · see citing works
Mayer, M. L., Vyklický, L., & Westbrook, G. (1989) · The Journal of Physiology · doi:10.1113/jphysiol.1989.sp017724 · Cited by 272 · see citing works
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 · see citing works
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 258 · see citing works
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 250 · see citing works
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 215 · see citing works
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 · see citing works
Holmgren, M., Shin, K. S., & Yellen, G. (1998) · Neuron · doi:10.1016/s0896-6273(00)80571-1 · Cited by 198 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Legendre, P., & Westbrook, G. L. (1990) · The Journal of Physiology · doi:10.1113/jphysiol.1990.sp018266 · Cited by 171 · see citing works
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 158 · see citing works
Sakurada, K., Masu, M., & Nakanishi, S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54166-1 · Cited by 154 · see citing works
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 · see citing works
Leonard, J. P., & Kelso, S. R. (1990) · Neuron · doi:10.1016/0896-6273(90)90443-j · Cited by 124 · see citing works
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 105 · see citing works
Fisher, J. L., & Macdonald, R. L. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02944.1998 · Cited by 102 · see citing works
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 · see citing works
Horenstein, J., & Akabas, M. H. (1998) · PubMed · Cited by 82 · see citing works
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 · see citing works
Flagged first, then by citations
1 of the 48 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- polyamines and activators of protein kinase C. Proc. Natl. Acad.
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 3,645 · see citing works
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 · see citing works
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 2,063 · see citing works
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 · see citing works
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 · see citing works
Structure, function, and allosteric modulation of NMDA receptors
Hansen, K. B., Yi, F., Perszyk, R. E., Furukawa, H., Wollmuth, L. P., Gibb, A. J., & Traynelis, S. F. (2018) · The Journal of General Physiology · doi:10.1085/jgp.201812032 · Cited by 574 · see citing works
The Actions of Synaptically Released Zinc at Hippocampal Mossy Fiber Synapses
Vogt, K. E., Mellor, J. R., Tong, G., & Nicoll, R. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)81149-6 · Cited by 491 · see citing works
Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates
Sullivan, N. J., Geisbert, T. W., Geisbert, J. B., Xu, L., Yang, Z., Roederer, M., Koup, R. A., Jahrling, P. B., & Nabel, G. J. (2003) · Nature · doi:10.1038/nature01876 · Cited by 464 · see citing works
Molecular basis of NMDA receptor functional diversity
Paoletti, P. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07628.x · Cited by 446 · see citing works
Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation
Choi, Y., Tenneti, L., Le, D. A., Ortiz, J., Bai, G., Chen, H.-S. V., & Lipton, S. A. (2000) · Nature Neuroscience · doi:10.1038/71090 · Cited by 426 · see citing works
Self-citationZinc at glutamatergic synapses
Paoletti, P., Vergnano, A. M., Barbour, B., & Casado, M. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.061 · Cited by 417 · see citing works
Movement of zinc and its functional significance in the brain
Takeda, A. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00044-8 · Cited by 416 · see citing works
Mony, L., Kew, J. N. C., Gunthorpe, M. J., & Paoletti, P. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00304.x · Cited by 404 · see citing works
The structure and function of glutamate receptor ion channels
Madden, D. R. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn725 · Cited by 381 · see citing works
Cysteine regulation of protein function – as exemplified by NMDA-receptor modulation
Lipton, S. A., Choi, Y.-B., Takahashi, H., Zhang, D., Li, W., Godzik, A., & Bankston, L. A. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02245-2 · Cited by 375 · see citing works
Self-citationMechanism of differential control of NMDA receptor activity by NR2 subunits
Gielen, M. C., Retchless, B. S., Mony, L., Johnson, J. W., & Paoletti, P. (2009) · Nature · doi:10.1038/nature07993 · Cited by 325 · see citing works
Hansen, K. B., Ogden, K. K., Yuan, H., & Traynelis, S. F. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.035 · Cited by 300 · see citing works
Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis
Hardingham, G. E., & Do, K. Q. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.19 · Cited by 304 · see citing works
Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2
Passafaro, M., Nakagawa, T., Sala, C., & Sheng, M. (2003) · Nature · doi:10.1038/nature01781 · Cited by 301 · see citing works
Li, Y., Hough, C. J., Suh, S. W., Sarvey, J. M., & Frederickson, C. J. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.86.5.2597 · Cited by 263 · see citing works
HIV‐1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity
Haughey, N. J., Nath, A., Mattson, M. P., Slevin, J. T., & Geiger, J. D. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00396.x · Cited by 258 · see citing works
The Micromolar Zinc-Binding Domain on the NMDA Receptor Subunit NR2B
Rachline, J., Perin-Dureau, F., Goff, A. L., Neyton, J., & Paoletti, P. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3967-04.2005 · Cited by 238 · see citing works
Modulation of Triheteromeric NMDA Receptors by N-Terminal Domain Ligands
Hatton, C. J., & Paoletti, P. (2005) · Neuron · doi:10.1016/j.neuron.2005.03.005 · Cited by 237 · see citing works
Control of NMDA Receptor Function by the NR2 Subunit Amino-Terminal Domain
Yuan, H., Hansen, K. B., Vance, K. M., Ogden, K. K., & Traynelis, S. F. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1365-09.2009 · Cited by 225 · see citing works
Molecular Organization of a Zinc Binding N-Terminal Modulatory Domain in a NMDA Receptor Subunit
Paoletti, P., Perin-Dureau, F., Fayyazuddin, A., Goff, A. L., Callebaut, I., & Neyton, J. (2000) · Neuron · doi:10.1016/s0896-6273(00)00163-x · Cited by 220 · see citing works
Zinc Dynamics and Action at Excitatory Synapses
Vergnano, A. M., Rebola, N., Savtchenko, L. P., Pinheiro, P. S., Casado, M., Kieffer, B. L., Rusakov, D. A., Mulle, C., & Paoletti, P. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.034 · Cited by 210 · see citing works
NMDA Receptors in the Central Nervous System
Hansen, K. B., Yi, F., Perszyk, R. E., Menniti, F. S., & Traynelis, S. F. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7321-7_1 · Cited by 206 · see citing works
Structure of the zinc‐bound amino‐terminal domain of the NMDA receptor NR2B subunit
Karakaş, E., Simorowski, N., & Furukawa, H. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.338 · Cited by 198 · see citing works
Insight into zinc signaling from dietary zinc deficiency
Takeda, A., & Tamano, H. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.09.003 · Cited by 195 · see citing works
Pan, E., Zhang, X., Huang, Z., Krężel, A., Zhao, M., Tinberg, C. E., Lippard, S. J., & McNamara, J. O. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.019 · Cited by 187 · see citing works
Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block
Dravid, S. M., Erreger, K., Yuan, H., Nicholson, K., Le, P., Lyuboslavsky, P., Almonte, A., Murray, E., Mosley, C., Barber, J., et al. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.124958 · Cited by 184 · see citing works
Mapping the Binding Site of the Neuroprotectant Ifenprodil on NMDA Receptors
Perin-Dureau, F., Rachline, J., Neyton, J., & Paoletti, P. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-14-05955.2002 · Cited by 183 · see citing works
Low, C., Zheng, F., Lyuboslavsky, P. N., & Traynelis, S. F. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.180307497 · Cited by 173 · see citing works
Allosteric modulators of NMDA receptors: multiple sites and mechanisms
Zhu, S., & Paoletti, P. (2014) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2014.10.009 · Cited by 167 · see citing works
Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines
Mony, L., Zhu, S., Carvalho, S., & Paoletti, P. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.203 · Cited by 168 · see citing works
Fayyazuddin, A., Villarroel, Á., Goff, A. L., Lerma, J., & Neyton, J. (2000) · Neuron · doi:10.1016/s0896-6273(00)81070-3 · Cited by 168 · see citing works
Redox modulation of the NMDA receptor
Choi, Y., & Lipton, S. A. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000638 · Cited by 165 · see citing works
Self-citationNelson, M. T., Woo, J., Kang, H., Vitko, I., Barrett, P. Q., Perez‐Reyes, E., Lee, J., Shin, H., & Todorovic, S. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1800-07.2007 · Cited by 158 · see citing works
Zinc Modulates Bidirectional Hippocampal Plasticity by Effects on NMDA Receptors
Izumi, Y., Auberson, Y. P., & Zorumski, C. F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1258-06.2006 · Cited by 152 · see citing works
Functional Insights from Glutamate Receptor Ion Channel Structures
Kumar, J., & Mayer, M. L. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183711 · Cited by 137 · see citing works
Molecular bases of NMDA receptor subtype‐dependent properties
Glasgow, N. G., Retchless, B. S., & Johnson, J. W. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.273763 · Cited by 138 · see citing works
Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor
Jalali‐Yazdi, F., Chowdhury, S. R., Yoshioka, C., & Gouaux, E. (2018) · Cell · doi:10.1016/j.cell.2018.10.043 · Cited by 134 · see citing works
Choi, Y.-B., Chen, H.-S. V., & Lipton, S. A. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00392.2001 · Cited by 132 · see citing works
Self-citationNR2B Signaling Regulates the Development of Synaptic AMPA Receptor Current
Hall, B. J., Ripley, B. A., & Ghosh, A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3793-07.2007 · Cited by 130 · see citing works
Whittle, N., Lübec, G., & Singewald, N. (2008) · Amino Acids · doi:10.1007/s00726-008-0195-6 · Cited by 124 · see citing works
Ogden, K. K., Chen, W., Swanger, S. A., McDaniel, M. J., Fan, L. Z., Hu, C., Tankovic, A., Kusumoto, H., Kosobucki, G. J., Schulien, A. J., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006536 · Cited by 124 · see citing works
Structural Rearrangements of NR1/NR2A NMDA Receptors during Allosteric Inhibition
Gielen, M. C., Goff, A. L., Stroebel, D., Johnson, J. W., Neyton, J., & Paoletti, P. (2008) · Neuron · doi:10.1016/j.neuron.2007.11.021 · Cited by 121 · see citing works
On the Hypes and Falls in Neuroprotection: Targeting the NMDA Receptor
Villmann, C., & Becker, C. (2007) · The Neuroscientist · doi:10.1177/1073858406296259 · Cited by 119 · see citing works
Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity
Manzerra, P., Behrens, M. M., Canzoniero, L. M. T., Wang, X. Q., Heidinger, V., Ichinose, T., Yu, S. P., & Choi, D. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191353598 · Cited by 118 · see citing works
Allosteric interaction between the amino terminal domain and the ligand binding domain of NR2A
Zheng, F., Erreger, K., Low, C. M., Banke, T. G., Lee, C. J., Conn, P. J., & Traynelis, S. F. (2001) · Nature Neuroscience · doi:10.1038/nn0901-894 · Cited by 117 · see citing works
Fluorescent zinc indicators for neurobiology
Thompson, R. B., Peterson, D. C., Mahoney, W., Cramer, M., Maliwal, B. P., Suh, S. W., Frederickson, C., Fierke, C. A., & Heřman, P. (2002) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(02)00144-9 · Cited by 116 · see citing works
Stys, P. K., You, H., & Zamponi, G. W. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.225276 · Cited by 115 · see citing works
Hypoxia Enhances S-Nitrosylation-Mediated NMDA Receptor Inhibition via a Thiol Oxygen Sensor Motif
Takahashi, H., Shin, Y., Cho, S.-J., Zago, W. M., Nakamura, T., Gu, Z., Ma, Y., Furukawa, H., Liddington, R., Zhang, D., et al. (2007) · Neuron · doi:10.1016/j.neuron.2006.11.023 · Cited by 108 · see citing works
Self-citationYuan, H., Erreger, K., Dravid, S. M., & Traynelis, S. F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414215200 · Cited by 107 · see citing works
Control of Assembly and Function of Glutamate Receptors by the Amino-Terminal Domain
Hansen, K. B., Furukawa, H., & Traynelis, S. F. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.067157 · Cited by 105 · see citing works
Molecular Determinants of Proton-Sensitive N-Methyl-d-aspartate Receptor Gating
Low, C., Lyuboslavsky, P. N., French, A. M., Le, P., Wyatte, K., Thiel, W. H., Marchan, E. M., Igarashi, K., Kashiwagi, K., Gernert, K. M., et al. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.6.1212 · Cited by 104 · see citing works
Tóth, K. (2011) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-072610-145218 · Cited by 101 · see citing works
Identification of an inhibitory Zn2+ binding site on the human glycine receptor α1 subunit
Harvey, R. J., Thomas, P., James, C., Wilderspin, A. F., & Smart, T. G. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.00053.x · Cited by 98 · see citing works
The role of histidine residues in modulation of the rat P2X2 purinoceptor by zinc and pH
Clyne, J. D., LaPointe, L. D., & Hume, R. I. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.013244 · Cited by 94 · see citing works
Protons Trap NR1/NR2B NMDA Receptors in a Nonconducting State
Banke, T. G., Dravid, S. M., & Traynelis, S. F. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3154-04.2005 · Cited by 87 · see citing works
Zinc Effects on NMDA Receptor Gating Kinetics
Amico-Ruvio, S. A., Murthy, S. E., Smith, T. P., & Popescu, G. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.02.042 · Cited by 86 · see citing works
Hernandez, A. R., Simorowski, N., Karakaş, E., & Furukawa, H. (2016) · Neuron · doi:10.1016/j.neuron.2016.11.006 · Cited by 84 · see citing works
Paul, S., & Connor, J. A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06835.x · Cited by 85 · see citing works
Interaction of metal ions with neurotransmitter receptors and potential role in neurodiseases
Marchetti, C. (2014) · BioMetals · doi:10.1007/s10534-014-9791-y · Cited by 84 · see citing works
pH-Dependent Inhibition of Kainate Receptors by Zinc
Mott, D. D., Benveniste, M., & Dingledine, R. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3567-07.2008 · Cited by 82 · see citing works
Moroni, M., Vijayan, R., Carbone, A. L., Zwart, R., Biggin, P. C., & Bermúdez, I. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1228-08.2008 · Cited by 81 · see citing works
Whittle, N., Hauschild, M., Lübec, G., Holmes, A., & Singewald, N. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0849-10.2010 · Cited by 81 · see citing works
Lin, C., & Lane, H. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00093 · Cited by 80 · see citing works
Bhattacharya, S., Khatri, A., Swanger, S. A., DiRaddo, J. O., Yi, F., Hansen, K. B., Yuan, H., & Traynelis, S. F. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.010 · Cited by 77 · see citing works
The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors
Nakagawa, T. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8149-x · Cited by 72 · see citing works
Nihei, M. K., & Guilarte, T. R. (2001) · NeuroToxicology · doi:10.1016/s0161-813x(01)00035-3 · Cited by 74 · see citing works
Separation of Domain Contacts Is Required for Heterotetrameric Assembly of Functional NMDA Receptors
Farina, A. N., Blain, K. Y., Maruo, T., Kwiatkowski, W., Choe, S., & Nakagawa, T. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6041-10.2011 · Cited by 72 · see citing works
Novel NMDA receptor modulators: an update
Santangelo, R., Acker, T. M., Zimmerman, S. S., Katzman, B. M., Strong, K. L., Traynelis, S. F., & Liotta, D. C. (2012) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2012.728587 · Cited by 72 · see citing works
Veran, J., Kumar, J., Pinheiro, P. S., Athané, A., Mayer, M. L., Perrais, D., & Mulle, C. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.027 · Cited by 70 · see citing works
Erreger, K., & Traynelis, S. F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.095497 · Cited by 69 · see citing works
Dynamic action of neurometals at the synapse
Tamano, H., & Takeda, A. (2011) · Metallomics · doi:10.1039/c1mt00008j · Cited by 68 · see citing works
Modulation of Neuronal Signal Transduction and Memory Formation by Synaptic Zinc
Sindreu, C. B., & Storm, D. R. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00068 · Cited by 67 · see citing works
Zinc inhibition of rat NR1/NR2AN‐methyl‐ d ‐aspartate receptors
Erreger, K., & Traynelis, S. F. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.143941 · Cited by 65 · see citing works
Takeda, A., Fuke, S., Ando, M., & Oku, N. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.009 · Cited by 65 · see citing works
Molecular Characterization of NMDA-Like Receptors inAplysiaandLymnaea:Relevance to Memory Mechanisms
Ha, T. J., Kohn, A. B., Bobkova, Y. V., & Moroz, L. L. (2006) · Biological Bulletin · doi:10.2307/4134562 · Cited by 65 · see citing works
Xiong, Z.-G., Pelkey, K. A., Lu, W. Y., Lu, Y. M., Roder, J., MacDonald, J. F., & Salter, M. W. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-j0003.1999 · Cited by 63 · see citing works
Lamtai, M., Chaibat, J., Ouakki, S., Zghari, O., Mesfioui, A., Hessni, A. E., Rifi, E. H., Marmouzi, I., Essamri, A., & Ouichou, A. (2018) · Brain Sciences · doi:10.3390/brainsci8080141 · Cited by 61 · see citing works
Cell type‐specific action of seizure‐induced intracellular zinc accumulation in the rat hippocampus
Côté, A., Chiasson, M., Peralta, M. R., Lafortune, K., Pellegrini, L., & Tóth, K. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.089458 · Cited by 59 · see citing works
NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain
Liu, Y., Li, Y., Fang, Z., Liao, H.-L., Zhang, Y., Lin, J., Liu, F., & Shen, J. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.999509 · Cited by 60 · see citing works
Madry, C., Mesic, I., Betz, H., & Laube, B. (2007) · Molecular Pharmacology · doi:10.1124/mol.107.040071 · Cited by 56 · see citing works
Zinc transporter‐1: a novel NMDA receptor‐binding protein at the postsynaptic density
Mellone, M., Pelucchi, S., Alberti, L. D., Genazzani, A. A., Luca, M. D., & Gardoni, F. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12968 · Cited by 55 · see citing works
Malherbe, P., Mutel, V., Broger, C., Perin-Dureau, F., Kemp, J. A., Neyton, J., Paoletti, P., & Kew, J. N. C. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.056291 · Cited by 55 · see citing works
Domnguez, M. I., Blasco‐Ibáñez, J. M., Crespo, C., Marqués‐Marí, A. I., & Mart�nez-Guijarro, F. J. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00731-5 · Cited by 55 · see citing works
Amino terminal domain regulation of NMDA receptor function
Herin, G. A., & Aizenman, E. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.07.015 · Cited by 55 · see citing works
Structural Basis of NR2B-Selective Antagonist Recognition by N-Methyl-d-aspartate Receptors
Mony, L., Krzaczkowski, L., Leonetti, M. D., Goff, A. L., Alarcon, K., Neyton, J., Bertrand, H.-O., Acher, F., & Paoletti, P. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.050971 · Cited by 53 · see citing works
Altered zinc sensitivity of NMDA receptors harboring clinically-relevant mutations
Serraz, B., Grand, T., & Paoletti, P. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.06.008 · Cited by 53 · see citing works
Molecular determinants of Pb2+ interaction with NMDA receptor channels
Gavazzo, P., Zanardi, I., Baranowska‐Bosiacka, I., & Marchetti, C. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.07.003 · Cited by 53 · see citing works
Structure and Function of the NMDA Receptor
Yuan, H., Geballe, M. T., Hansen, K. B., & Traynelis, S. F. (2008) · Springer eBooks · doi:10.1007/978-0-387-77232-5_11 · Cited by 47 · see citing works
Yuan, H., Vance, K. M., Junge, C., Geballe, M. T., Snyder, J. P., Hepler, J. R., Yepes, M., Low, C., & Traynelis, S. F. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m805123200 · Cited by 46 · see citing works
Suppression by Zinc of AMPA Receptor-Mediated Synaptic Transmission in the Retina
Zhang, D.-Q., Ribelayga, C., Mangel, S. C., & McMahon, D. G. (2002) · Journal of Neurophysiology · doi:10.1152/jn.2002.88.3.1245 · Cited by 45 · see citing works
Lorca, R. A., Coddou, C., Gazitúa, M. C., Bull, P., Arredondo, C., & Huidobro-Toro, J. P. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03387.x · Cited by 44 · see citing works
Properties of Triheteromeric N-Methyl-d-Aspartate Receptors Containing Two Distinct GluN1 Isoforms
Yi, F., Zachariassen, L. G., Dorsett, K. N., & Hansen, K. B. (2018) · Molecular Pharmacology · doi:10.1124/mol.117.111427 · Cited by 39 · see citing works
Structural role of zinc ions bound to postsynaptic densities
Jan, H., Chen, I., Tsai, Y., & Chang, Y. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01093.x · Cited by 40 · see citing works
The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders
Lee, K. C., Mills, Z., Cheung, P. Y., Cheyne, J. E., & Montgomery, J. M. (2022) · Pharmaceuticals · doi:10.3390/ph16010001 · Cited by 40 · see citing works
Sirrieh, R. E., MacLean, D. M., & Jayaraman, V. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.482356 · Cited by 37 · see citing works
- 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
