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Cited by 819Neuroscience and Neuropharmacology ResearchIon channel regulation and functionNicotinic Acetylcholine Receptors Study

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

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Ascher, P, Nowak, L·1988·The Journal of Physiology
DOI 10.1113/jphysiol.1988.sp017078PMC PMC1191662
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Abstract

1. 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. 2. In nominally Mg2+‐free solutions the opening and closing of the channels leads to rectangular current pulses, the mean duration of which varies little with membrane potential. After addition of Mg2+, the single‐channel currents recorded at negative potentials appear in bursts of short openings separated by brief closures. 3. The duration of the short openings decreases with increasing Mg2+ concentration, while the duration of the short closures is independent of the Mg2+ concentration. Depolarization increases the duration of the short openings and decreases the duration of the short closures. 4. The dependence of the burst structure on the Mg2+ concentration and on membrane potential is compatible to a first approximation with a model in which Mg2+ ions enter the open channel and block it by binding at a deep site. A better approximation requires, however, additional assumptions such as Mg2+ permeation and/or interactions between Ca2+ and Mg2+. 5. Increasing the extracellular Ca2+ concentration from 1 to 100 mM produces three effects on the currents flowing through NMDA channels. It shifts the reversal potential towards a positive value (+30 mV); it reduces the outward current flowing through the NMDA channels at very positive potentials; it reduces the inward current flowing at negative potentials. 6. The interpretation of the effects of Ca2+ appears to require three hypotheses: that Ca2+ permeates the NMDA channel, that there exists a significant surface potential at the entrance of the NMDA channel in physiological solutions and that both Ca2+ and monovalent cations bind to the channel, binding being stronger in the case of Ca2+ ions. 7. While Co2+ and, to a lesser extent, Mn2+ mimic the effects of Mg2+ on the NMDA channel, Ca2+, Ba2+ and Cd2+ do not. The distinction between Mg2+‐like and Ca2+‐like divalent cations corresponds to a difference in the speed of exchange of the water molecules surrounding the cations in solutions. Thus, it is possible that permeation occurs for all the divalent cations, but is slower for those which are slowly dehydrated.

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  • NMDARs are highly permeable to Ca2+.

    “The discovery that NMDARs are highly permeable to Ca2+ (179, 180)”

    From Synaptic memory and CaMKII (2023) · cites this paper as [180]

    The paper’s numbered summary (points 5–6; page not available in our copy) reports a calcium-dependent reversal-potential shift and concludes that Ca2+ permeates NMDA channels. It does not characterize or quantify that permeability as high, so it supports calcium permeability but not the claim’s degree. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Ascher, P., & Nowak, L.
Affiliations
École Normale Supérieure - PSL (FR)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
1988-05
Volume
399
Issue
1
Pages
247-266
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.1988.sp017078
PMC
PMC1191662
OpenAlex
W1533559637
Cited by
819
References
1
Citations by year
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FWCI
19.71
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
NMDA receptor, divalent cations, magnesium, calcium, single-channel currents, channel gating, channel block, reversal potential, cation permeation, cation binding sites, cation exchange
MeSH terms
Animals, Calcium, Cells, Cultured, Electrophysiology, Ion Channels, Magnesium, Neurons, Receptors, N-Methyl-D-Aspartate, Receptors, Neurotransmitter, Mice

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