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

Nature. 1986 May 29-Jun 4;321(6069):519-22. doi: 10.1038/321519a0.

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 triggering increases in intracellular free Ca2+.

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / pharmacology
  • Calcium / metabolism*
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Embryo, Mammalian
  • Mice
  • N-Methylaspartate
  • Neurons / drug effects
  • Neurons / metabolism*
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / physiology*
  • Spinal Cord / metabolism*

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Aspartic Acid
  • N-Methylaspartate
  • Calcium