NSF (N-ethylmaleimide-sensitive factor) is an adenosine triphosphatase
(ATPase) that contributes to a protein complex essential for membrane
fusion. The synaptic function of this protein was investigated by inj
ecting, into the giant presynaptic terminal of squid, peptides that in
hibit the ATPase activity of NSF stimulated by the soluble NSF attachm
ent protein (SNAP). These peptides reduced the amount and slowed the k
inetics of neurotransmitter release as a result of actions that requir
ed vesicle turnover and occurred at a step subsequent to vesicle docki
ng. These results define NSF as an essential participant in synaptic v
esicle exocytosis that regulates the kinetics of neurotransmitter rele
ase and, thereby, the integrative properties of synapses.