PRESYNAPTIC GLUTAMATE RECEPTORS DEPRESS INHIBITORY POSTSYNAPTIC TRANSMISSION IN LOBSTER NEUROMUSCULAR SYNAPSE

1. We examined the functional role of a GTP-coupled glutamate receptor (Glu(B) 2. Injection of guanosine 5'-O-(3-thiotriphosphate)(GTPgammaS), a hydrolysis-resistant analogue of GTP, into the excitatory axon mimicked the presynaptic glutamate response and effectively suppressed excitatory postsynaptic potentials or excitatory postsynaptic currents (EPSCs). 3. Statistical analysis revealed that the coefficient of variation (standard deviation divided by the mean of EPSC amplitude) was increased after injection of GTPgammaS into the excitatory axon, indicating a presynaptic inhibition of transmitter release. 4. The effect of glutamate on inhibitory postsynaptic potentials (IPSPs) or inhibitory postsynaptic currents (IPSCs) was studied when the postsynaptic glutamate receptors were blocked by the Joro spider toxin (JSTX). Glutamate depressed IPSPs or IPSCs in the JSTX-treated preparation. Furthermore, repetitive stimulation of the excitatory nerve produced effective inhibition of IPSCs. 5. Quisqualate and kainate suppressed IPSCs in a similar way to glutamate. In contrast, N-methyl-D-aspartate, ibotenic acid, trans-D,L-1-amino-1,3-cyclopentanedicarboxyloc acid, and 2-amino-4-phosphonobutanate had no effect on Glu(B)-R. 6. Our results indicate that Glu(B)-R, which exists in both excitatory and inhibitory nerve terminals, regulates transmitter release by a presynaptic inhibitory mechanism.