ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Protons trap NR1/NR2B NMDA receptors in a nonconducting state.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
- Inhibition of delta-1 glutamate receptor current by extracellular protons.bioRxiv : the preprint server for biology · 2026Article
- Article
- GluD receptors are functional ion channels.Biophysical journal · 2023Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- GluN2A and GluN2B NMDA receptors use distinct allosteric routes.Nature communications · 2021Article
- TwoeLife · 2021Article
- Article
- Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity.International journal of molecular sciences · 2020Review
- Structure, function, and allosteric modulation of NMDA receptors.The Journal of general physiology · 2018Review
- Kinetic models for activation and modulation of NMDA receptor subtypes.Current opinion in physiology · 2018Article
- Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.Nature communications · 2018Article
- NMDA Receptors in the Central Nervous System.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Acid-sensing ion channel 1a drives AMPA receptor plasticity following ischaemia and acidosis in hippocampal CA1 neurons.The Journal of physiology · 2015Article
- Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders.Pharmacology & therapeutics · 2015Review
- Article
- Actions of bupivacaine, a widely used local anesthetic, on NMDA receptor responses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Extracellular Ca(2+) ions reduce NMDA receptor conductance and gating.The Journal of general physiology · 2014Article
- GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord.Scientific reports · 2014Article
- Endosomal pH in neuronal signaling and synaptic transmission: role of Na(+)/H(+) exchanger NHE5.Frontiers in physiology · 2014Review
- NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease.Nature reviews. Neuroscience · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
NMDA receptors are highly expressed in the CNS and are involved in excitatory synaptic transmission, as well as synaptic plasticity. Given that overstimulation of NMDA receptors can cause cell death, it is not surprising that these channels are under tight control by a series of inhibitory extracellular ions, including zinc, magnesium, and H+. We studied the inhibition by extracellular protons of recombinant NMDA receptor NR1/NR2B single-channel and macroscopic responses in transiently transfected human embryonic kidney HEK 293 cells using patch-clamp techniques. We report that proton inhibition proceeds identically in the absence or presence of agonist, which rules out the possibility that protonation inhibits receptors by altering coagonist binding. The response of macroscopic currents in excised patches to rapid jumps in pH was used to estimate the microscopic association and dissociation rates for protons, which were 1.4 x 10(9) m(-1) sec(-1) and 110-196 sec(-1), respectively (K(d) corresponds to pH 7.2). Protons reduce the open probability without altering the time course of desensitization or deactivation. Protons appear to slow at least one time constant describing the intra-activation shut-time histogram and modestly reduce channel open time, which we interpret to reflect a reduction in the overall channel activation rate and possible proton-induced termination of openings. This is consistent with a modest proton-dependent slowing of the macroscopic response rise time. From these data, we propose a physical model of proton inhibition that can describe macroscopic and single-channel properties of NMDA receptor function over a range of pH values.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.