Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+.

The effects of extracellular applications of Zn2+ ions on the strychnine-sensitive glycine receptor were studied in cultured rat spinal cord neurons and with recombinant glycine receptors expressed in human embryonic kidney 293 cells. Nanomolar concentrations of Zn2+ enhanced the chloride ion current in response to brief applications of 100 microM glycine. The enhancement of glycine responses increased from 20 nM to 1 microM Zn2+. Higher concentrations of Zn2+ caused a reversal of the potentiation, followed by progressive inhibition of the glycine response up to approximately 20-50 microM Zn2+. The biphasic modulation by Zn2+ appeared essentially identical in native and recombinant glycine receptors. Biphasic Zn2+ modulation was observed both with picrotoxin-insensitive heteromeric (alpha 2/beta) receptors and with picrotoxin-sensitive homomeric receptors consisting only of alpha 2 subunits. This suggests that the alpha subunit alone is sufficient for formation of two distinct Zn2+ binding sites on the glycine receptor. The demonstration of Zn2+ modulation of the strychnine-sensitive glycine receptor is of potential physiological importance, in view of the likely range of subsynaptic Zn2+ concentrations to which the receptor is exposed.

• Publication year

  1994

• Venue

  Molecular Pharmacology

• Publication date

  1994-12-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0026-895x(25)09863-3PMID 7808436
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Mutagenesis rescues spermine and Zn2+ potentiation of recombinant NMDA receptors.

  1994cited by this paper
• Zn2+: an endogenous modulator of ligand- and voltage-gated ion channels.

  1994cited by this paper
• Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.

  1993cited by this paper
• Zn2+ potentiates ATP-activated currents in rat sympathetic neurons

  1993cited by this paper
• Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo‐ and hetero‐oligomers.

  1993cited by this paper
• Zinc enhances GABAergic transmission in rat neocortical neurons.

  1993cited by this paper
• A novel modulatory binding site for zinc on the GABAA receptor complex in cultured rat neurones.

  1992cited by this paper
• Enhancement of gamma‐aminobutyric acid‐activated Cl‐ currents in cultured rat hippocampal neurones by three volatile anaesthetics.

  1992cited by this paper
• Zinc, a neurotoxin to cultured neurons, contaminates cycad flour prepared by traditional guamanian methods

  1992cited by this paper
• Induction of giant depolarizing potentials by zinc in area CA1 of the rat hippocampus does not result from block of GABAB receptors.

  1992cited by this paper
• The atypical M2 segment of the beta subunit confers picrotoxinin resistance to inhibitory glycine receptor channels.

  1992cited by this paper
• Noncompetitive inhibition of gamma-aminobutyric acidA channels by Zn.

  1991cited by this paper
• A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission

  1991cited by this paper
• Ligand-gated ion channels in the brain: the amino acid receptor superfamily.

  1990cited by this paper
• Functional properties of recombinant rat GABAA receptors depend upon subunit composition.

  1990cited by this paper
• Cloning and expression of the 58 kd beta subunit of the inhibitory glycine receptor.

  1990cited by this paper
• Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes.

  1990cited by this paper
• Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+.

  1990cited by this paper
• Transient expression shows ligand gating and allosteric potentiation of GABAA receptor subunits.

  1988cited by this paper
• Zinc neurotoxicity in cortical cell culture.

  1988cited by this paper
• Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer.

  1988cited by this paper
• Primary culture of identified neurons from the visual cortex of postnatal rats

  1986cited by this paper
• Release of endogenous Zn2+ from brain tissue during activity

  1984cited by this paper
• Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat.

  1983cited by this paper
• Zinc concentrations in the cerebrospinal fluid of normal adults and patients with neurological diseases.

  1982cited by this paper
• Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches

  1981cited by this paper

• An emerging role for synaptic Zn2+ in substance use disorders.

  2026cites this paper
• Mechanisms underlying modulation of human GlyRα3 by Zn2+ and pH

  2024cites this paper
• Methods for negating the impact of zinc contamination to allow characterization of positive allosteric modulators of glycine receptors

  2024cites this paper
• Evolutionary conservation of Zinc-Activated Channel (ZAC) functionality in mammals: a range of mammalian ZACs assemble into cell surface-expressed functional receptors

  2023cites this paper
• Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies

  2022cites this paper
• Glycine Receptors in Spinal Nociceptive Control—An Update

  2021cites this paper
• Different Behaviors of a Glycine Receptor Channel Pore Residue between Wild-Type-Mimicking and Disease-Type-Mimicking Formats.

  2021cites this paper
• The function and regulation of zinc in the brain.

  2021cites this paper
• Glycine receptors in GtoPdb v.2021.3

  2021cites this paper
• Modulation of recombinant human alpha 1 glycine receptor by flavonoids and gingerols

  2021cites this paper
• Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC)

  2021cites this paper
• Modulators of the inhibitory glycine receptor.

  2020cites this paper
• Glutamate, D -( 2 )-2-Amino-5-Phosphonopentanoic Acid, and N -Methyl- D -Aspartate Do Not Directly Modulate Glycine Receptors

  2020cites this paper
• Glutamate, AP5 and NMDA do not directly modulate glycine receptors.

  2020cites this paper
• Differential roles of extracellular Histidine residues of GPR68 for proton-sensing and allosteric modulation by divalent metal ions.

  2020cites this paper
• A loss-of-function mutation of an inhibitory zinc- and proton-binding site reduces channel blocker potency in the glycine receptor.

  2019cites this paper
• Modulation of Glycine Receptor-Mediated Pain Signaling in vitro and in vivo by Glucose

  2019cites this paper
• Modulation of inhibitory and excitatory neurotransmissions by Zn2+ on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice.

  2019cites this paper
• General Physiology and Biophysics Revised manuscript #1 Title: Modulation of inhibitory and excitatory neurotransmissions by Zn2+ on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice Running title: Modulation of neurotransmitters by Zn2+ on the SG neurons

  2019cites this paper
• Cellular / Molecular The Glycine Transporter GlyT 2 Controls the Dynamics of Synaptic Vesicle Refilling in Inhibitory Spinal Cord Neurons

  2019influential citation
• Glycine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

  2019cites this paper
• Interactions between Zinc and Allosteric Modulators of the Glycine Receptor

  2017cites this paper
• Glycine Receptor Drug Discovery.

  2017cites this paper
• Zinc as a Neuromodulator in the Central Nervous System with a Focus on the Olfactory Bulb

  2017cites this paper
• Murine startle mutant Nmf11 affects the structural stability of the glycine receptor and increases deactivation

  2016cites this paper
• Functional modulation of glycine receptors by the alkaloid gelsemine

  2016cites this paper
• Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors

  2016cites this paper
• Receptors in Embryonic Mouse Hippocampal Neurons

  2016cites this paper
• Identification and characterization of heptapeptide modulators of the glycine receptor.

  2016cites this paper
• The Free Zinc Concentration in the Synaptic Cleft of Artificial Glycinergic Synapses Rises to At least 1 μM

  2016cites this paper
• Genuine open form of the pentameric ligand-gated ion channel GLIC.

  2015cites this paper
• Functional reconstitution of glycinergic synapses incorporating defined glycine receptor subunit combinations.

  2015cites this paper
• Molecular Physiology of Glycine Receptors in Vertebrate Nervous Systems

  2015cites this paper
• NeuronsReceptors in Embryonic Mouse Hippocampal

  2015cites this paper
• Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission.

  2015cites this paper
• Disruption of zinc neuromodulation by Aß oligomers: therapeutic implications.

  2014cites this paper
• Glycine and GABAA Ultra-Sensitive Ethanol Receptors as Novel Tools for Alcohol and Brain Research

  2014cites this paper
• Zinc interactions with allosteric modulators at the glycine receptor

  2014influential citation
• Properties and Regulation of GABA A and Glycine Receptor Channels

  2014cites this paper
• The GLRA1 Missense Mutation W170S Associates Lack of Zn2+ Potentiation with Human Hyperekplexia

  2013cites this paper
• Zinc-dependent modulation of α2- and α3-glycine receptor subunits by ethanol.

  2013cites this paper
• Restoring ionotropic inhibition as an analgesic strategy.

  2013cites this paper
• Mutation of a Zinc-Binding Residue in the Glycine Receptor α1 Subunit Changes Ethanol Sensitivity In Vitro and Alcohol Consumption In Vivo

  2013cites this paper
• Exploration of the Protective Effects of Some Natural Compounds against Neurodegeneration Exploiting Glycine Receptors in vivo Model

  2013cites this paper
• Probing the pharmacological properties of distinct subunit interfaces within heteromeric glycine receptors reveals a functional ββ agonist‐binding site

  2012cites this paper
• Discovery of a Novel Allosteric Modulator of 5-HT3 Receptors

  2012cites this paper
• Effect of subchronic zinc toxicity on rat salivary glands and serum composition

  2012cites this paper
• Fast synaptic inhibition in spinal sensory processing and pain control.

  2012cites this paper
• Ligand-gated ion channels: new insights into neurological disorders and ligand recognition.

  2012cites this paper
• Regulation of Glucagon Secretion in Normal and Diabetic Human Islets by γ-Hydroxybutyrate and Glycine*

  2012cites this paper
• Molecular Basis of Inhibitory Modulation of P2X2 Receptors by Zinc and Copper.

  2012cites this paper
• Synaptic physiology revised: think zinc!

  2012cites this paper
• Zinc modulation of glycine receptors.

  2011cites this paper
• Allosteric modulation of glycine receptors

  2011cites this paper
• Identification of novel allosteric modulators of the glycine receptor using phage display technology

  2011cites this paper
• Zinc enhances long‐term potentiation through P2X receptor modulation in the hippocampal CA1 region

  2011cites this paper
• Potentiation and inhibition of glycine receptors by tutin.

  2011cites this paper
• Molecular targets and mechanisms for ethanol action in glycine receptors.

  2010cites this paper
• Binding, activation and modulation of Cys-loop receptors.

  2010cites this paper
• Glycine and glycine receptor signaling in hippocampal neurons: diversity, function and regulation.

  2010cites this paper
• Identification of Novel Specific Allosteric Modulators of the Glycine Receptor Using Phage Display*

  2010cites this paper
• Loop 2 Structure in Glycine and GABAA Receptors Plays a Key Role in Determining Ethanol Sensitivity*

  2009cites this paper
• Localization of zip1 and zip4 mRNA in the adult rat brain

  2009cites this paper
• Presynaptic glycine receptors facilitate spontaneous glutamate release onto hilar neurons in the rat hippocampus

  2009cites this paper
• Zinc Signaling in Neuronal Tolerance

  2009cites this paper
• Binding-site mutations in the alpha1 subunit of the inhibitory glycine receptor convert the inhibitory metal ion Cu2+ into a positive modulator.

  2009cites this paper
• Recombinant glycine receptors: stoichiometry and kinetics

  2009cites this paper
• Mutations within the agonist-binding site convert the homomeric α1 glycine receptor into a Zn2+-activated chloride channel

  2008cites this paper
• Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors

  2008cites this paper
• Zinc potentiates neuronal nicotinic receptors by increasing burst duration.

  2008cites this paper
• Molecular Organization of the Postsynaptic Membrane at Inhibitory Synapses

  2008cites this paper
• pH-Dependent Inhibition of Kainate Receptors by Zinc

  2008cites this paper
• Mapping a molecular link between allosteric inhibition and activation of the glycine receptor

  2008cites this paper
• Zinc modulation of glycine receptors in acutely isolated rat CA3 neurons.

  2008cites this paper
• The Glycine Transporter GlyT2 Controls the Dynamics of Synaptic Vesicle Refilling in Inhibitory Spinal Cord Neurons

  2008influential citation
• Aluminium-induced electrophysiological, biochemical and cognitive modifications in the hippocampus of aging rats.

  2008cites this paper
• The glycine transporter GlyT 2 controls the dynamics of synaptic vesicle refilling in inhibitory spinal cord neurons

  2008influential citation
• Glycine Receptor a1

  2008cites this paper
• Effects of a mutation in the TM2-TM3 linker region of the glycine receptor alpha1 subunit on gating and allosteric modulation.

  2007cites this paper
• Dissecting the Facilitator and Inhibitor Allosteric Metal Sites of the P2X4 Receptor Channel

  2007cites this paper
• Molecular pharmacology of the glycine receptor chloride channel.

  2007influential citation
• Zinc enhances the inhibitory effects of strychnine-sensitive glycine receptors in mouse hippocampal neurons.

  2007cites this paper
• The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons.

  2007cites this paper
• GABA and glycine as neurotransmitters: a brief history

  2006cites this paper
• Modulating inhibitory ligand-gated ion channels

  2006cites this paper
• Zn2+ modulation of neurotransmitter transporters.

  2006cites this paper
• Modulation of inhibitory glycine receptors in cultured embryonic mouse hippocampal neurons by zinc, thiol containing redox agents and carnosine.

  2006cites this paper
• Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission.

  2006cites this paper
• Molecular Basis for Zinc Potentiation at Strychnine-sensitive Glycine Receptors*

  2005cites this paper
• Molecular determinants of glycine receptor αβ subunit sensitivities to Zn2+‐mediated inhibition

  2005influential citation
• Molecular mechanisms of alcohol and volatile anesthetic modulation of glycine receptor function

  2005cites this paper
• The neurobiology of zinc in health and disease

  2005cites this paper
• Molecular determinants of glycine receptor alphabeta subunit sensitivities to Zn2+-mediated inhibition.

  2005cites this paper
• Molecular interactions of zinc with the glycine receptor

  2005influential citation
• Levetiracetam: an innovative and cost-effective add-on drug for refractory partial epilepsy

  2004cites this paper
• Changes on the properties of glycine receptors during neuronal development.

  2004cites this paper
• Antisense Evidence for Nuclear Factor-κB–Dependent Embryopathies Initiated by Phenytoin-Enhanced Oxidative Stress

  2004cites this paper
• Insights From Endogenous and Engineered Zn2+ Binding Sites in Monoamine Transporters

  2004cites this paper
• Endogenous zinc inhibits GABA(A) receptors in a hippocampal pathway.

  2004cites this paper
• The two-pore-domain K(+) channels TREK-1 and TASK-3 are differentially modulated by copper and zinc.

  2004cites this paper