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Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block
Article first published online: 4 MAY 2007
DOI: 10.1113/jphysiol.2006.124958
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Dravid, S. M., Erreger, K., Yuan, H., Nicholson, K., Le, P., Lyuboslavsky, P., Almonte, A., Murray, E., Mosley, C., Barber, J., French, A., Balster, R., Murray, T. F. and Traynelis, S. F. (2007), Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block. The Journal of Physiology, 581: 107–128. doi: 10.1113/jphysiol.2006.124958
Publication History
- Issue published online: 4 MAY 2007
- Article first published online: 4 MAY 2007
- (Received 14 November 2006; accepted after revision 8 February 2007; first published online 15 February 2007)
References
- , & (1989). N-Methyl-d-aspartate antagonists: ready for clinical trial in brain ischemia? Ann Neurol 25, 398–403. Direct Link:
- , , , , , & (1999). Characterization of MK-801-induced behavior as a putative rat model of psychosis. J Pharmacol Exp Ther 290, 1393–1408.
- , & (1998). Binding sites for permeant ions in the channel of NMDA receptors and their effects on channel block. Nat Neurosci 1, 451–461.
- & (1999). Permeant ion regulation of N-methyl-d-aspartate receptor channel block by Mg2+. Proc Natl Acad Sci U S A 96, 14571–14576.
- (1991). Drug abuse potential evaluation in animals. Br J Addict 86, 1549–1558.
- & (1988). Receptor mediation of the discriminative stimulus properties of phencyclidine and σ-opioid agonists. Psychopharmacol Ser 4, 122–135.
- , & (2005). Protons trap NR1/NR2B NMDA receptors in a nonconducting state. J Neurosci 25, 42–51.
- (2004). Disposition of Toxic Drugs and Chemicals in Man, 7th edn. Biomedical Publications, Foster City , CA , USA .
- & (1992). Effect of extracellular pH on the potency of N-methyl-d-aspartic acid receptor competitive antagonists. Mol Pharmacol 42, 679–686.
- , , & (1997). Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol 77, 309–323.
- , & (2005). Amantadine inhibits NMDA receptors by accelerating channel closure during channel block. J Neurosci 25, 3312–3322.
- , , & (2003). Determinants of trapping block of N-methyl-d-aspartate receptor channels. J Neurochem 87, 56–65.
- (1989). Memantine is a potent blocker of N-methyl-d-aspartate (NMDA) receptor channels. Eur J Pharmacol 166, 591–592.
- & (1977). The behavior of 9-aminoacridine as an indicator of transmembrane pH difference in liposomes of natural bacterial phospholipids. J Bioenerg Biomembr 9, 17–29.
- & (1992). Modulation of pH by neuronal activity. Trends Neurosci 15, 396–402.
- (1985). Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci Lett 58, 293–297.
- (1992). Excitotoxic cell death. J Neurobiol 23, 1261–1276. Direct Link:
- & (1999). Identification and mechanism of action of two histidine residues underlying high-affinity Zn2+ inhibition of the NMDA receptor. Neuron 23, 171–180.
- , & (1988). The neuroprotective action of ketamine and MK-801 after transient cerebral ischemia in rats. Anesthesiology 69, 702–709.
- & (2006). NMDA receptor NR2 subunit dependence of the slow component of magnesium unblock. J Neurosci 26, 5825–5834.
- & (1994). Dynamics of the actions of tetrahydro-9-aminoacridine and 9-aminoacridine on glutamatergic currents: concentration-jump studies in cultured rat hippocampal neurons. J Pharmacol Exp Ther 268, 503–514.
- & (1998). Open channel block and alteration of N-methyl-d-aspartic acid receptor gating by an analog of phencyclidine. Biophys J 75, 1801–1816.
- , , & (1999). The glutamate receptor ion channels. Pharmacol Rev 51, 7–61.
- , & (1999). Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22, 391–397.
- , & (2004). Brevetoxin activation of voltage-gated sodium channels regulates Ca dynamics and ERK1/2 phosphorylation in murine neocortical neurons. J Neurochem 89, 739–749.
- (1995). The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioural and anatomical models of the dementias. Brain Res Brain Res Rev 20, 250–267.
- & (1991). Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-d-aspartate. Eur J Pharmacol 198, 215–217.
- , , & (2004). Glutamate receptor gating. Crit Rev Neurobiol 16, 187–224.
- , , , & (2005a). Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles. J Physiol 563, 345–358.
- , , , , & (2005b). Mechanism of partial agonism at NMDA receptors for a conformationally restricted glutamate analog. J Neurosci 25, 7858–7866.
- , & (1991). MK-801 and related compounds in monkeys: discriminative stimulus effects and effects on a conditional discrimination. J Pharmacol Exp Ther 257, 727–734.
- , , , , & (1998). Influence of urine pH and urinary flow on the renal excretion of memantine. Br J Clin Pharmacol 46, 541–546.
- & (1991). Effects of MK-801 stereoisomers on schedule-controlled behavior in rats. Psychopharmacology (Berl) 105, 477–480.
- & (1997). Dizocilpine-like discriminative stimulus effects of competitive NMDA receptor antagonists in mice. Psychopharmacology (Berl) 133, 43–50.
- , , & (1990). Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures. Brain Res 506, 339–342.
- , & (1987). Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. J Neurosci 7, 3343–3349.
- , & (1989). The mechanism of action and pharmacological specificity of the anticonvulsant NMDA antagonist MK-801: a voltage clamp study on neuronal cells in culture. Br J Pharmacol 96, 480–494.
- , , , & (2003). Evaluation of the NR2B-selective NMDA receptor antagonist Ro 63-1908 on rodent behaviour: evidence for an involvement of NR2B NMDA receptors in response inhibition. Neuropharmacology 44, 324–341.
- (1977). The pH-dependent rate of action of local anesthetics on the node of Ranvier. J Gen Physiol 69, 475–496.
- , & (1989). Comparison of the behavioural and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine. Eur J Pharmacol 166, 359–366.
- (1990). Caffeine as a model drug of abuse. Trends Pharmacol Sci 11, 355–356.
- & (1988). Block of N-methyl-d-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci U S A 85, 1307–1311.
- (1992). High probability opening of NMDA receptor channels by l-glutamate. Science 255, 470–472.
- & (2001). Glutamate receptor subunit expression in primary neuronal and secondary glial cultures. J Neurochem 77, 1457–1474.
- & (2006). Mechanism of action of memantine. Curr Opin Pharmacol 6, 61–67.
- , , , & (1997). Block and modulation of N-methyl-d-aspartate receptors by polyamines and protons: role of amino acid residues in the transmembrane and pore-forming regions of NR1 and NR2 subunits. Mol Pharmacol 52, 701–713.
- , , & (1991). NMDA antagonist inhibits rapid tolerance to ethanol. Brain Res Bull 26, 643–645.
- , & (1991). Pharmacologic studies of the neuroprotective actions of a glutamate antagonist in ischemia. J Neurotrauma 8, 175–186.
- , & (1990). N-Methyl-d-aspartate antagonism and phencyclidine-like activity: a drug discrimination analysis. J Pharmacol Exp Ther 253, 1017–1025.
- & (1987). Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Meth 20, 83–90.
- , , & (1994). Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl 43, 91–104.
- , & (1999). The changing landscape of ischaemic brain injury mechanisms. Nature 399, A7–A14.
- , , , & (2005). Differential binding properties of [3H]dextrorphan and [3H]MK-801 in heterologously expressed NMDA receptors. Neuropharmacology 49, 1–16.
- , , , , , & (1998). Developmental changes in localization of NMDA receptor subunits in primary cultures of cortical neurons. Eur J Neurosci 10, 1704–1715.
- , , , , , , , , , , , & (2003). Molecular determinants of proton-sensitive N-methyl-d-aspartate receptor gating. Mol Pharmacol 63, 1212–1222.
- , , & (2000). Molecular determinants of coordinated proton and zinc inhibition of N-methyl-d-aspartate NR1/NR2A receptors. Proc Natl Acad Sci U S A 97, 11062–11067.
- , , , , , , & (1991). Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neurones. J Physiol 432, 483–508.
- & (1990). Mechanisms of blockade of excitatory amino acid receptor channels. Trends Pharmacol Sci 11, 167–172.
- , & (1999). Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res 36, 189–204.
- , & (2004). Clarke's Analysis of Drugs and Poisons, 3rd edn, vol. 2. Pharmaceutical Press, London .
- , & (1998). Molecular determinants of NMDA receptor pharmacological diversity. Prog Brain Res 116, 171–190.
- & (1997). NR1 and NR2 subunit contributions to N-methyl-d-aspartate receptor channel blocker pharmacology. J Pharmacol Exp Ther 280, 614–620.
- , , & (1992). Identification by mutagenesis of a Mg2+-block site of the NMDA receptor channel. Nature 358, 673–675.
- , , , , , , & (1998). Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition. Nat Neurosci 1, 659–667.
- , , & (2001). Open probability of homomeric murine 5-HT3A serotonin receptors depends on subunit occupancy. J Physiol 535, 427–443.
- (2003). Phencyclidine – effects on human performance and behavior. Forensic Sci Rev 15, 61–74.
- , , , , , & (2006). pH dependence of phosphono-derivative NMDA receptor antagonists. Abstract Viewer and Itinerary Planner, prog. no. 623.2. Society for Neuroscience 2006 Online.
- , , & (1991). Dynamics of interstitial and intracellular pH in evolving brain infarct. Am J Physiol Regul Integr Comp Physiol 260, R581–R588.
- , & (1999). Evaluation of the reinforcing properties and phencyclidine-like discriminative stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys. Psychopharmacology (Berl) 146, 49–59.
- & (1997). Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury? J Neurotrauma 14, 677–698.
- & (1997). Influence of extracellular pH on inhibition by ifenprodil at N-methyl-d-aspartate receptors in Xenopus oocytes. Neurosci Lett 225, 29–32.
- , , , & (1988). The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Ann Neurol 24, 543–551. Direct Link:
- , , , & (1993). Patch clamp studies on the kinetics and selectivity of N-methyl-d-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology 32, 1337–1350.
- , , & (1989). In vivo demonstration of the enhancement of MK-801 by l-glutamate. Life Sci 44, 1593–1599.
- , , , & (2005). Structural locus of the pH gate in the Kir1.1 inward rectifier channel. Biophys J 88, 2597–2606.
- , , & (1998). Distinct influx pathways, not calcium load, determine neuronal vulnerability to calcium neurotoxicity. J Neurochem 71, 2349–2364.
- & (2001). Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol 24, 107–129.
- , , , , , , , , & (1999). pH gating of ROMK (Kir1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome. Proc Natl Acad Sci U S A 96, 15298–15303.
- , & (1977). Local anesthetics. Effect of pH on use-dependent block of sodium channels in frog muscle. Biophys J 20, 343–368.
- , , & (1994). pH-metric log P. 4. Comparison of partition coefficients determined by HPLC and potentiometric methods to literature values. J Pharm Sci 83, 1280–1283. Direct Link:
- & (2002). Blocker studies of the functional architecture of the NMDA receptor channel. Neurosci Behav Physiol 32, 157–171.
- , & (1999). Probing of NMDA channels with fast blockers. J Neurosci 19, 10611–10626.
- (1988). Transport of amantadine and rimantadine through the blood–brain barrier. J Pharmacol Exp Ther 244, 516–519.
- , , & (1992). Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. Proc Biol Sci 250, 271–277.
- , & (1990). Modulation of the N-methyl-d-aspartate channel by extracellular H+. Proc Natl Acad Sci U S A 87, 6445–6449.
- & (1996). A review of NMDA receptors and the phencyclidine model of schizophrenia. Pharmacotherapy 16, 82–93.
- & (1993). Evolving concepts about the role of acidosis in ischemic neuropathology. J Neurochem 61, 793–803.
- , , , & (1998). Control of voltage-independent zinc inhibition of NMDA receptors by the NR1 subunit. J Neurosci 18, 6163–6175.
- & (1990). Proton inhibition of N-methyl-d-aspartate receptors in cerebellar neurons. Nature 345, 347–350.
- & (1991). Pharmacological properties and H+ sensitivity of excitatory amino acid receptor channels in rat cerebellar granule neurones. J Physiol 433, 727–763.
- & (1997). Control of rat GluR6 glutamate receptor open probability by protein kinase A and calcineurin. J Physiol 503, 513–531.
- , , , & (1989). The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. Eur J Pharmacol 167, 127–135.
- , & (1990). The effect of external pH changes on responses to excitatory amino acids in mouse hippocampal neurones. J Physiol 430, 497–517.
- & (2005). NMDA/NR2B selective antagonists in the treatment of ischemic brain injury. Curr Drug Targets CNS Neurol Disord 4, 143–151.
- , & (1997). Discriminative stimulus effects of site-selective N-methyl-d-aspartate antagonists in NPC 17742-trained rats and squirrel monkeys. Psychopharmacology (Berl) 132, 382–388.
- & (1988). Phencyclidine-like discriminative stimulus properties of MK-801 in rats. Eur J Pharmacol 146, 167–169.
- , & (1998). Intracellular Mg2+ interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel. J Physiol 506, 33–52.
- , , , , & (1986). The anticonvulsant MK-801 is a potent N-methyl-d-aspartate antagonist. Proc Natl Acad Sci U S A 83, 7104–7108.
- , , , , & (2000). A single residue contributes to the difference between Kir4.1 and Kir1.1 channels in pH sensitivity, rectification and single channel conductance. J Physiol 528, 267–277.
- , & (2000). N-Methyl-d-aspartate receptor channel block by meperidine is dependent on extracellular pH. Anesth Analg 90, 928–932.
- , , , , , & (2000). Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH. J Gen Physiol 116, 33–45.
- , , & (2005). Conserved structural and functional control of N-methyl-d-aspartate receptor gating by transmembrane domain M3. J Biol Chem 280, 29708–29716.
- & (1995). Structural basis for explaining open-channel blockade of the NMDA receptor. J Neurosci 15, 1446–1454.
- , , , , , & (2001). Allosteric interaction between the amino terminal domain and the ligand binding domain of NR2A. Nat Neurosci 4, 894–901.
- & (2001). Na+ occupancy and Mg2+ block of the N-methyl-d-aspartate receptor channel. J Gen Physiol 117, 275–286.

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