The neurotoxin, β-N-methylamino-l-alanine (BMAA) interacts with the strychnine-insensitive glycine modulatory site of the N-methyl-d-aspartate receptor

Electrophysiological and receptor binding techniques were used to determine whether the neurotoxin β-N-4-methylamino-l-alanine (BMAA), a monocarboxylic amino acid, can act at the strychnine-insensitive glycine modulatory site to modify the activity of N-methyl-d-aspartate receptors. dl-BMAA but not l-BMAA reversibly potentiated the amplitude of NMDA-activated currents. Neither dl-BMAA nor l-BMAA were able independently to activate currents. The reversal potential and the potential-dependence of the amplitude were not affected by dl-BMAA. The dl-BMAA effect was reversibly antagonized by 7-chlorokynurenic acid. Concentration jump experiments showed that the time course of the "off" response of NMDA-activated currents in the presence of dl-BMAA is faster than in the presence of glycine, suggesting that dl-BMAA dissociates from the receptor more rapidly than glycine. dl-BMAA produced a concentration-dependent displacement of [³H]glycine binding which was additive with that of 7-chlorokynurenic acid. These data indicate that d-BMAA could act as a stereospecific modulator of NMDA receptor function by acting as an agonist at the strychnine-insensitive glycine modulatory site of the NMDA receptor.