Magnesium gates glutamate-activated channels in mouse central neurones

  title={Magnesium gates glutamate-activated channels in mouse central neurones},
  author={Linda M. Nowak and Piotr Bregestovski and Philippe Ascher and Alain Herbet and Alain Prochiantz},
The responses of vertebrate neurones to glutamate involve at least three receptor types1. One of these, the NMDA receptor (so called because of its specific activation by N-methyl-D-aspartate), induces responses presenting a peculiar voltage sensitivity2–6. Above resting potential, the current induced by a given dose of glutamate (or NMDA) increases when the cell is depolarized4–6. This is contrary to what is observed at classical excitatory synapses, and recalls the properties of ‘regenerative… 

Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones

Using voltage-clamp experiments on mouse spinal cord neurones, it is shown that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (∼1 mM) of Mg2+ from the extracellular fluid, providing further evidence that Mg 2+ blocks inward current flow through ion channels linked to NMDA receptors.

Glutamate activates multiple single channel conductances in hippocampal neurons

Four or more distinct single-channel currents are evoked by applying glutamate to each outside-out membrane patch, which are compatible with the model that all the single channel conductances activated by glutamate reflect the operation of one or two complex molecular entities.

NMDA receptor activation by spontaneous glutamatergic neurotransmission.

Results indicate that NMDA receptors significantly contribute to signaling at rest in the absence of dendritic depolarizations or concomitant AMPA receptor activity.

Effect of zinc on NMDA receptor-mediated channel currents in cortical neurons

  • C. ChristineD. Choi
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1990
The channel block produced by Zn2+ was faster than that of Mg2+, which at 100 microM and negative membrane voltages induces flickering of the NMDA receptor-activated channel without changing apparent channel amplitude.

Divalent Cations as Modulators of NMDA-Receptor Channels on Mouse Central Neurons

The term neuromodulation usually implies some combination of peptide or catecholamine neurotransmitters and a second messenger such as cAMP which together produce a response with a rather slow time course, but recent studies of conductance mechanisms activated by L-glutamate on mammalian neurons indicate that their behavior may be substantially more complex.

Glycine potentiates the NMDA response in cultured mouse brain neurons

G glycine may facilitate excitatory transmission in the brain through an allosteric activation of the NMDA receptor, and can be observed in outside-out patches as an increase in the frequency of opening of the channels activated by NMDA agonists.

NMDA receptors activate the arachidonic acid cascade system in striatal neurons

It is reported here that glutamate and NMDA, acting at typicalNMDA receptors, stimulate the release of arachidonic acid from striatal neurons probably by stimulation of a Ca2+-dependent phospholipase A2, and it is suggested that NMDA receptors are the postsynaptic receptors which trigger the synthesis of these putative transynaptic messengers.

NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones

It is directly demonstrated that excitatory amino acids acting at NMDA receptors on spinal cord neurones increase the intracellular Ca2+ activity, measured using the indicator dye arsenazo III, and that this is the result of Ca2- influx through NMDA receptor channels.

Modulation by magnesium of the affinity of NMDA receptors for glycine in murine hippocampal neurones.

Mg2+ can enhance NMDA‐mediated currents and reduce desensitization of this receptor by allosterically interacting with the glycine binding site and this interaction may be a key physiological mechanism through which modulation of the NMDA receptor is achieved.



Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations.

From the similarity in action between Mg2+ and the D‐alpha‐aminoadipate group of NMDA antagonists, it is suggested that the central depressant action of low concentrations of Mg1+ involves predominantly a postsynaptically mediated interference with the action of an excitatory amino acid transmitter.

N-methyl-D-aspartate-type receptors mediate striatal 3H-acetylcholine release evoked by excitatory amino acids

Investigating the effects of specific excitatory amino acid receptor agonists and antagonists on the release of 3H-acetylcholine from slices of the rat corpus striatum finds that excitatories amino acid analogues evoke a tetrodotoxin-sensitive release from rat striatal slices superfused in Mg2+-free medium, NMDA and ibotenate being the most potent and kainate and quisqualate the least potent.

The actions of excitatory amino acids on motoneurones in the feline spinal cord.

The results for the mechanism of excitatory transmission is discussed and it is concluded that the DLH response is probably mediated via a decrease in K+ conductance and that the availability of this conductance channel is potential dependent.

Permeability of the post‐synaptic membrane of an excitatory glutamate synapse to sodium and potassium.

  • R. Anwyl
  • Biology
    The Journal of physiology
  • 1977
It is proposed that the outward K current is dependent upon the inward Na current, and that the increase in K permeability is abolished in zero external Na.

Interaction of Tetraethylammonium Ion Derivatives with the Potassium Channels of Giant Axons

A number of compounds related to TEA+ (tetraethylammoniumion) were injected into squid axons and their effects on g K (the potassium conductance) were determined, suggesting that K+ ions traverse the membrane by way of pores, and they cannot be explained by the usual type of carrier model.

Local anaesthetics transiently block currents through single acetylcholine‐receptor channels.

It is concluded that drug molecules reversibly block open end‐plate channels and that the flickering within a burst represents this fast, repeatedly occurring reaction.

L‐glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction.

It is concluded that L‐glutamate is, or is an agonist of, the excitatory transmitter at certain Drosophila larval neuromuscular junctions.

The mode of action of antagonists of the excitatory response to acetylcholine in Aplysia neurones.

The mode of action of various antagonists of acetylcholine (ACh) excitatory effects on Aplysia neurones was studied under voltage clamp, supporting the hypothesis that the binding site of the antagonists is linked to the ionic channel.