High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons

John R. Pace, Martin Brian, Steven M. Paul, Michael A Rogawski

Research output: Contribution to journalArticle

41 Scopus citations


High concentrations (30 μM-5 mM) of the neutral amino acids l-serine, l-cysteine, l-alanine, l-proline and glycine elicited inward current responses when applied to hippocampal neurons patch clamped at -60 mV in the presence of 1-10 μM glycine and 1 μM strychnine. The amplitude of the response to l-serine increased in a concentration-dependent fashion within the range 0.1-10 mM (EC50, 2.6 mM). l-Serine (1 mM) currents were attenuated by Mg2+ (100 μM) and completely blocked by the competitive N-methyl-d-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (30 μM). The CPP block could be overcome by raising the concentration of l-serine. We conclude that high concentrations of some neutral amino acids activate NMDA receptor-coupled ion channels by acting as agonists at the NMDA recognition site.

Original languageEnglish (US)
Pages (from-to)97-100
Number of pages4
JournalNeuroscience Letters
Issue number1
StatePublished - Jul 6 1992
Externally publishedYes



  • Alanine
  • Cysteine
  • Glycine
  • Hippocampal neuron
  • N-Methyl-d-aspartate receptor
  • Proline
  • Serine

ASJC Scopus subject areas

  • Neuroscience(all)

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