Voltage-dependent block by intracellular Mg2+ of N-methyl-D-aspartate-activated channels.

@article{Johnson1990VoltagedependentBB,
  title={Voltage-dependent block by intracellular Mg2+ of N-methyl-D-aspartate-activated channels.},
  author={J. W. Johnson and Philippe Ascher},
  journal={Biophysical journal},
  year={1990},
  volume={57 5},
  pages={
          1085-90
        }
}
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Permeant ion regulation of N-methyl-D-aspartate receptor channel block by Mg(2+).

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The model provides an explanation for the strength of the voltage dependence of Mg(o)(2+) block and quantifies the interdependence of permanent and blocking ion binding to NMDA receptors.

Dual Block by Mg2+ of the N-Methyl-D-Aspartate-Activated Channel

Two groups of glutamate receptors mediating fast excitatory neurotransmission can be clearly distinguished; the best studied group is specifically activated by N-methyl-D-aspartate (NMDA), and the second group, which is probably more heterogeneous, exhibits very little voltage dependence.

PERMEANT ION AND SUBUNIT DEPENDENCE OF EXTERNAL Mg2+ BLOCK OF NMDA RECEPTORS

Mg2+ inhibition of whole-cell NMDA currents in cortical neurons, which express NMDA receptors with NR2A or NR2B NR2 subunits, is very sensitive to ionic conditions and can be explained by a kinetic model which incorporates external permeant ion binding sites within the pore.

Intracellular Mg2+ interacts with structural determinants of the narrow constriction contributed by the NR1‐subunit in the NMDA receptor channel

It is concluded that intracellular Mg2+ interacts with residues that form the narrow constriction in the NMDA receptor channel with the N‐site asparagine of the NR1‐subunit representing the dominant blocking site, although the two blocking sites are positioned very close to each other.

Ionic flow enhances low‐affinity binding: a revised mechanistic view into Mg2+ block of NMDA receptors

The flow or the tendency of movement of the permeant ions may actually enhance rather than interfere with Mg2+ block, making the unique current–voltage relationship of NMDAR and the molecular basis of many important neurobiological phenomena.

Effects of intracellular Mg2+ on channel gating and steady‐state responses of the NMDA receptor in cultured rat neurons.

A four‐state model in which the NMDA‐activated channel can close while blocked by Mgi2+ is proposed, and it is estimated that the rate of channel opening is increased by a factor of 1.4 when Mg2+ occupies the channel.

Ionic permeability characteristics of the N-methyl-D-aspartate receptor channel

Permeability-ratio measurements in mixtures of monovalent and divalent cations indicated that local charges in or near the pore do not produce a large local surface potential in physiologic solutions, and the mechanism for the high Ca2+ conductance of the NMDA receptor channel is not the same as for the voltage-dependent Ca 2+ channel (VDCC).

NMDA Receptor Complex Blockade by Oral Administration of Magnesium: Comparison with MK-801

Competitive blockage of the sodium channel by intracellular magnesium ions in central mammalian neurones

It is reported here that permeation across the sodium channel is voltage- and concentration-dependently reduced by Mgi2+.

Glutamate and glycine decrease the affinity of [3H]MK-801 binding in the presence of Mg2+.

...

35 References

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.

The role of divalent cations in the N‐methyl‐D‐aspartate responses of mouse central neurones in culture.

Single‐channel currents activated by N‐methyl‐D‐aspartate (NMDA) agonists were analysed in the presence of various extracellular concentrations of divalent cations in outside‐out patches from mouse neurones in primary culture to investigate the effects of Ca2+ on currents flowing through NMDA channels.

Magnesium gates glutamate-activated channels in mouse central neurones

The voltage dependence of the NMDA receptor-linked conductance appears to be a consequence of the voltage dependenceof the Mg2+ block and its interpretation does not require the implication of an intramembrane voltage-dependent ‘gate’.

Ionic Blockage of Sodium Channels in Nerve

A voltage-dependent block of sodium channels by hydrogen ions is explained, which shifts the responses of sodium channel "gates" to voltage, probably by altering the surface potential of the nerve.

Intracellular magnesium blocks sodium outward currents in a voltage- and dose-dependent manner.

Dual effects of intracellular magnesium on muscarinic potassium channel current in single guinea‐pig atrial cells.

Intracellular Mg2+, at a physiological concentration, has a dual action on the muscarinic K+ channel: first M g2+ activates the channel in the presence of GTP through GTP‐binding proteins (G proteins), and secondly it blocks outward currents through the channel, thereby causing the inwardly rectifying property.

The effects of magnesium upon adenosine triphosphate‐sensitive potassium channels in a rat insulin‐secreting cell line.

It is concluded that internal Mg2+ ions cause the rectification of the K+‐ATP channel current‐voltage relationship and are required for K+-ATP channels activity to be maintained by a phosphorylation process and are needed for K-ATp channel activity evoked by ADP, GTP and GDP.

N‐methyl‐D‐aspartate‐activated channels of mouse central neurones in magnesium‐free solutions.

The whole‐cell and outside‐out configurations of the patch‐clamp method were used to investigate the properties of the channels activated by N‐methyl‐D‐aspartate (NMDA channels) in mouse central neurones in culture and it was observed that the single‐channel current amplitude varies linearly as a function of membrane potential between ‐80 and +60 mV.

Monovalent and divalent cation permeation in acetylcholine receptor channels. Ion transport related to structure

Single channel patch-clamp techniques were used to study nicotinic acetylcholine receptors in cultured rat myotubes, and the results are consistent with the channel having long, wide, multiply occupied vestibules that serve as transition zones to the short, selective, singly occupied narrow region of the channel.

The action of N‐methyl‐D‐aspartic acid on mouse spinal neurones in culture.

The voltage‐dependent block ofNMDA responses produced by physiological concentrations of Mg2+ is sufficient to explain the apparent increase in membrane resistance produced by NMDA in current‐clamp experiments, and the ability of NMDA to support repetitive firing.