ArticleThe Journal of physiology2002
Modulation by permeant ions of Mg(2+) inhibition of NMDA-activated whole-cell currents in rat cortical neurons.
Article in The Journal of physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Magnesium Ions as Modulators of Voltage-Gated and Ligand-Gated Ion Channels in Central Neurons.International journal of molecular sciences · 2025Review
- Genetic Causal Associations between Various Serum Minerals and Risk of Depression: A Mendelian Randomization Study.Actas espanolas de psiquiatria · 2024Article
- Inhibition of NMDA receptors through a membrane-to-channel path.Nature communications · 2022Article
- Interplay between Gating and Block of Ligand-Gated Ion Channels.Brain sciences · 2020Review
- Magnesium Acts as a Second Messenger in the Regulation of NMDA Receptor-Mediated CREB Signaling in Neurons.Molecular neurobiology · 2020Article
- Structure, function, and allosteric modulation of NMDA receptors.The Journal of general physiology · 2018Review
- New Cav2 calcium channel gating modifiers with agonist activity and therapeutic potential to treat neuromuscular disease.Neuropharmacology · 2018Article
- Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.Nature communications · 2018Article
- Article
- NMDA Receptors in the Central Nervous System.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Synaptic Variability Introduces State-Dependent Modulation of Excitatory Spinal Cord Synapses.Neural plasticity · 2015Article
- Frequency-dependent facilitation of synaptic throughput via postsynaptic NMDA receptors in the nucleus of the solitary tract.The Journal of physiology · 2015Article
- Mutant LRRK2 enhances glutamatergic synapse activity and evokes excitotoxic dendrite degeneration.Biochimica et biophysica acta · 2014Article
- Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation.Organogenesis · 2014Article
- Mechanistic and structural determinants of NMDA receptor voltage-dependent gating and slow Mg2+ unblock.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- HSV delivery of a ligand-regulated endogenous ion channel gene to sensory neurons results in pain control following channel activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Glutamate receptor ion channels: structure, regulation, and function.Pharmacological reviews · 2010Review
- Ionic flow enhances low-affinity binding: a revised mechanistic view into Mg2+ block of NMDA receptors.The Journal of physiology · 2010Article
- Voltage-dependent gating of NR1/2B NMDA receptors.The Journal of physiology · 2008Article
- Mg2+ and memantine block of rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes.The Journal of physiology · 2008Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Whole-cell N-methyl-D-aspartate (NMDA)-activated currents were recorded from cultured rat cortical neurons. We report here a powerful effect of changing permeant ion concentrations on the voltage-dependent inhibition by external Mg(2+) (Mg(2+)(o)) of these currents. Internal Cs(+) (Cs(+)(i)) affected Mg(2+)(o) inhibition of the NMDA-activated currents in a voltage-dependent manner. A decrease in Cs(+)(i) concentration ([Cs(+)](i)) from 125 to 8 mM reduced Mg(2+)(o) IC(50) by 1.4-fold at -105 mV and by 11.5-fold at -15 mV. A decrease in external Na(+) (Na(+)(o)) concentration ([Na(+)](o)) also reduced Mg(2+)(o) IC(50). This effect was voltage independent. A decrease in [Na(+)](o) from 140 to 70 mM reduced Mg(2+)(o) IC(50) by 1.4-fold at -105 mV and by 1.6-fold at -15 mV. Varying external Ca(2+) (Ca(2+)(o)) concentrations ([Ca(2+)](o)) from 0.1 to 1 mM did not affect Mg(2+)(o) inhibition, even though changing [Ca(2+)](o) in the same range strongly influenced the magnitude of NMDA-activated currents in the absence of Mg(2+)(o). However, increasing [Ca(2+)](o) to higher concentrations (2-20 mM) greatly increased Mg(2+)(o) IC(50) at hyperpolarized voltages. These data are consistent with a model in which Na(+)(i) and Cs(+)(i) modulate Mg(2+)(o) inhibition of NMDA-activated currents by occupying external permeant ion binding sites. The Mg(2+)(o) IC(50) values reported here are similar to Mg(2+)(o) K(D) values calculated from previous single-channel measurements of Mg(2+)(o) blocking kinetics. This similarity implies that Mg(2+)(o) does not affect gating while blocking the channel.
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