Activity-dependent neurotransmitter release kinetics: correlation with changes in morphological distributions of small and large vesicles in central nerve terminals
Agm. Leenders et al., Activity-dependent neurotransmitter release kinetics: correlation with changes in morphological distributions of small and large vesicles in central nerve terminals, EUR J NEURO, 11(12), 1999, pp. 4269-4277
In central nerve terminals transmitter release is tightly regulated and tho
ught to occur in a number of steps. These steps include vesicle mobilizatio
n and docking prior to neurotransmitter release. Intrasynaptic changes in v
esicle distribution were determined by electron microscopical analysis and
neurotransmitter release was monitored by biochemical measurements. We corr
elated K+-induced changes in distribution of small and large vesicles with
the release of their transmitters. For small synaptic vesicles, amino acid
release as well as recruitment to and docking at the active zone were activ
ated within 1 s of depolarization. In contrast, the disappearance of large
dense-cored vesicles and the release of the neuropeptide cholecystokinin we
re much slower, and no docking was observed. Studies with diverse Ca2+ chan
nel blockers indicated that mobilization and neurotransmitter release from
both vesicle types were regulated by multiple Ca2+ channels, although in di
fferent ways. Neurotransmitter release from small synaptic vesicles was pre
dominantly regulated by P-type Ca2+ channels, whereas primarily Q-type Ca2 channels regulated neurotransmitter release from large dense-cored vesicle
s. The different Ca2+ channnel types directly regulated mobilization of and
neurotransmitter release from small synaptic vesicles whereas, by their co
operativity in raising the intracellular Ca2+ concentration above release t
hreshold, they more indirectly regulated large dense-cored vesicle exocytos
is.