Letter | Published:

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

Nature volume 321, pages 519522 (29 May 1986) | Download Citation

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Abstract

Excitatory amino acids act via receptor subtypes in the mammalian central nervous system (CNS)1–3. 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 cations4–7. Various experiments suggest that Ca2+ flux is also associated with the activation of excitatory amino-acid receptors on vertebrate neurones8–11. 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+ channels12 while it enters and blocks NMDA receptor channels4,5,7,13,14. 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+ channels5,7. 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 triggering increases in intracellular free Ca2+.

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Author information

Affiliations

  1. Laboratory of Neurophysiology, NINCDS, National Institutes of Health, Bethesda, Maryland 20892, USA

    • Amy B. MacDermott
  2. Laboratory of Developmental Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA

    • Mark L. Mayer
    • , Gary L. Westbrook
    •  & Jeffery L. Barker
  3. Section of Molecular Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA

    • Stephen J. Smith
  4. Present address: Howard Hughes Medical Institute, Columbia University, CPS, 722 West 168th Street, New York, New York 10032, USA.

    • Amy B. MacDermott

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https://doi.org/10.1038/321519a0

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