Cited by 1,835Neuroscience and Neuropharmacology ResearchIon channel regulation and functionAmino Acid Enzymes and Metabolism

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

MacDermott, Amy B., Mayer, Mark L., Westbrook, Gary L., Smith, Stephen J., Barker, Jeffery L.·1986·Nature

DOI 10.1038/321519a0

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Abstract

Excitatory amino acids act via receptor subtypes in the mammalian central nervous system (CNS). The receptor selectively activated by N-methyl-D-aspartic acid (NMDA) has been best characterized using voltage-clamp and single-channel recording; the results suggest that NMDA receptors gate channels that are permeable to Na+, K+ and other monovalent cations. Various experiments suggest that Ca2+ flux is also associated with the activation of excitatory amino-acid receptors on vertebrate neurones. Whether Ca2+ enters through voltage-dependent Ca2+ channels or through excitatory amino-acid-activated channels of one or more subtype is unclear. Mg2+ can be used to distinguish NMDA-receptor-activated channels from voltage-dependent Ca2+ channels, because at micromolar concentrations Mg2+ has little effect on voltage-dependent Ca2+ channels while it enters and blocks NMDA receptor channels. Marked differences in the potency of other divalent cations acting as Ca2+ channel blockers compared with their action as NMDA antagonists also distinguish the NMDA channel from voltage-sensitive Ca2+ channels. However, we now directly demonstrate 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. Kainic acid (KA), which acts at another subtype of excitatory amino-acid receptor, was much less effective in trigge…

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Authors: MacDermott, A. B., Mayer, M. L., Westbrook, G. L., Smith, S. J., & Barker, J. L.
Affiliations: National Institutes of Health (US)
Yale University (US)
ORCID: Mayer, Mark L.
Westbrook, Gary L.
Smith, Stephen J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1986-05
Volume: 321
Issue: 6069
Pages: 519-522
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/321519a0
OpenAlex: W2010926499
Cited by: 1,835
References: 30
Citations by year: 2026: 8 · 2025: 11 · 2024: 14 · 2023: 12 · 2022: 13 · 2021: 15 · 2020: 18 · 2019: 22 · 2018: 15 · 2017: 17 · 2016: 19 · 2015: 20 · 2014: 29 · 2013: 23 · 2012: 24
FWCI: 40.51
Type: journal article
Language: en
Update notices: correction (1986-06-26)
correction (1986-06-26)
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (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 › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords: NMDA receptor, glutamate receptors, intracellular calcium, calcium influx, spinal cord neurons, kainic acid, voltage-gated calcium channels, magnesium block, arsenazo III, excitatory amino acid antagonists
MeSH terms: Animals, Aspartic Acid, Calcium, Cells, Cultured, Cytoplasm, Embryo, Mammalian, Neurons, Spinal Cord, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Receptors, Neurotransmitter, Mice

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

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