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.
- Hippocampal neuron
- N-Methyl-d-aspartate receptor