GLUTAMATE DEPRESSES RELEASE BY ACTIVATING NONCONVENTIONAL GLUTAMATE RECEPTORS AT CRAYFISH NERVE-TERMINALS

The present study shows that release of glutamate from crayfish nerve terminals is inhibited at low depolarizing current pulses by glutamate , N-methyl-D-aspartate (NMDA) and quisqualate. These agonists elicit i nhibitory effects at concentrations as low as 10(-8) M (quisqualate) a nd 10(-7) M (glutamate and NMDA). The NMDA-mediated inhibition is bloc ked by (+/-)-2-amino-5-phosphonovaleric acid (APV). The quisqualate-me diated inhibition is blocked by 6-cyano-7-nitroquinoxaline-2,3-dione ( CNQX). Both CNQX and APV are needed to block glutamate-mediated inhibi tion. The inhibition of release is not accompanied by a detectable cha nge in presynaptic membrane conductance at the secondary branch. Using fura-2, Ca2+ accumulation during repetitive stimulation (100 Hz) was monitored in single release boutons. Inhibition of release, elicited b y 10(-4) M glutamate, was not associated with a reduction in the accum ulation of Ca2+. We show that the glutamate released from a single or a few release boutons during normal activity acts similarly to glutama te added externally, i.e. it inhibits its own release.