NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones
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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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 [179]
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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)
- Venue
- Nature
- Published
- 1986-05
- Volume
- 321
- Issue
- 6069
- Pages
- 519-522
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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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