NERVE terminals are unique among cellular secretory systems in that th
ey can sustain vesicular release at a high rate. Although little is kn
own about the mechanisms that account for the distinctive features of
neurotransmitter release, it can be assumed that neuron-specific prote
ins are involved. One such protein family, the synapsins, are believed
to regulate neurotransmitter release through phosphorylation-dependen
t interactions with synaptic vesicles and cytoskeletal elements(1). He
re we show that clusters of vesicles at synaptic release sites are com
posed of two pools, a distal pool containing synapsin and a proximal p
ool devoid of synapsin and located adjacent to the presynaptic membran
e. Presynaptic injection of synapsin antibodies resulted in the loss o
f the distal pool, without any apparent effect on the proximal pool. D
epletion of this distal pool,vas associated with a marked depression o
f neurotransmitter release evoked by high-frequency (18-20 Hz) but not
by low-frequency (0.2 Hz) stimulation. Thus the availability of the s
ynapsin-associated pool of vesicles seems to be required to sustain re
lease of neurotransmitter in response to high-frequency bursts of impu
lses.