HIGH-CONCENTRATIONS OF NEUTRAL AMINO-ACIDS ACTIVATE NMDA RECEPTOR CURRENTS IN RAT HIPPOCAMPAL-NEURONS

High concentrations (30-mu-M-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-mu-M glycine and 1-mu-M 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-mu-M) and completely blocked by the competitive N-methyl-D-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (30-mu-M). 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.