Guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are involved
in exocytosis, endocytosis, and recycling of vesicles in yeast and mammalia
n secretory cells. However, little is known about their contribution to fas
t synaptic transmission. We Loaded guanine nucleotide analogs directly into
a giant nerve terminal in rat brainstem slices. Inhibition of G-protein ac
tivity had no effect on basal synaptic transmission, but augmented synaptic
depression and significantly slowed recovery from depression. A nonhydroly
zable GTP analog blocked recovery of transmission from activity-dependent d
epression. Neither effect was accompanied by a change in presynaptic calciu
m currents. Thus, G proteins contribute to fast synaptic transmission by re
fitting synaptic vesicles depleted after massive exocytosis.