NMDA receptors at excitatory synapses in the hippocampus: test of a theory of magnesium block

doi:10.1016/0304-3940(93)90443-O

Neuroscience Letters

Volume 156, Issues 1–2, 25 June 1993, Pages 73-77

https://doi.org/10.1016/0304-3940(93)90443-O Get rights and content

Abstract

Excitatory postsynaptic currents (EPSCs) were studied using the whole-cell patch-clamp technique to record from rat hippocampal pyramidal neurons in both slices and dissociated cultures. The voltage- and magnesium-dependence of the $N- methyl- d -aspartate$ (NMDA) component of the EPSCs was quantified by measuring the amplitude of this component at a range of holding potentials (−80 mV to 60 or 80 mV) in several bath magnesium concentrations (0.2μM, 0.1, 1 and 10 mM). All of our results were well-fitted by a theory of magnesium block developed from single-channel studies of extrajunctional NMDA channels in culture. It is concluded that extrasynaptic and subsynaptic NMDA channels both in culture and in situ have identical properties of magnesium block.

References (20)

L.M. Nowak et al.
Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg²⁺-free solutions
Neuron
(1992)
A.D. Randall et al.
Whole-cell patch-clamp recordings of an NMDA receptor-mediated synaptic current in rat hippocampal slices
Neurosci. Lett.
(1990)
P. Ascher et al.
The role of divalent cations in the $N- methyl- d -aspartate$ responses of mouse central neurons in culture
J. Physiol.
(1988)
P. Brehm et al.
Development and regulation of acetylcholine receptor function
J.M. Bekkers et al.
NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus
Nature
(1989)
J.M. Bekkers et al.
Presynaptic mechanism for long-term potentiation in the hippocampus
Nature
(1990)
I.D. Forsythe et al.
Slow excitatory postsynaptic currents mediated by $N- methyl- d -aspartate$ receptors on cultured mouse central neurones
J. Physiol.
(1988)
S. Hestrin et al.
Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices
J. Physiol.
(1990)
G.D.S. Hirst et al.
Transmission at autonomic neuroeffector junctions
Trends Neurosci.
(1992)
C.E. Jahr et al.
Glutamate activates multiple single channel conductances in hippocampal neurons
Nature
(1987)

There are more references available in the full text version of this article.

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NMDA receptors at excitatory synapses in the hippocampus: test of a theory of magnesium block

Abstract

Neuron

Neurosci. Lett.

The role of divalent cations in the N-methyl-d-aspartate responses of mouse central neurons in culture

J. Physiol.

Development and regulation of acetylcholine receptor function

NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus

Nature

Presynaptic mechanism for long-term potentiation in the hippocampus

Nature

Slow excitatory postsynaptic currents mediated by N-methyl-d-aspartate receptors on cultured mouse central neurones

J. Physiol.

Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices

J. Physiol.

Transmission at autonomic neuroeffector junctions

Trends Neurosci.

Glutamate activates multiple single channel conductances in hippocampal neurons

Nature

The role of divalent cations in the $N- methyl- d -aspartate$ responses of mouse central neurons in culture

Slow excitatory postsynaptic currents mediated by $N- methyl- d -aspartate$ receptors on cultured mouse central neurones