THE NEUROTOXIN, BETA-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 beta-N-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 [H-3]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.