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The Journal of Neuroscience, January 15, 2001, 21(2):462-476
Quantitative Relationship between Transmitter Release and Calcium
Current at the Calyx of Held Synapse
Takeshi
Sakaba and
Erwin
Neher
Max-Planck-Institute for Biophysical Chemistry, Department of
Membrane Biophysics, D-37077, Göttingen, Germany
A newly developed deconvolution method (Neher and Sakaba,
2001) allowed us to resolve the time course of neurotransmitter release at the calyx of Held synapse and to quantify some basic aspects
of transmitter release. First, we identified a readily releasable pool
(RRP) of synaptic vesicles. We found that the size of the RRP, when
tested with trains of strong stimuli, was constant regardless of the
exact stimulus patterns, if stimuli were confined to a time interval of
~60 msec. For longer-lasting stimulus patterns, recruitment of new
vesicles to the RRP made a substantial contribution to the total
release. Second, the cooperativity of transmitter release as a function
of Ca2+ current was estimated to be 3-4, which
confirmed previous results (Borst and Sakmann, 1999; Wu et al., 1999).
Third, an initial small Ca2+ influx increased the
efficiency of Ca2+ currents in subsequent
transmitter release. This type of facilitation was blocked by a high
concentration of EGTA (0.5 mM). Fourth, the release rates
of synaptic vesicles at this synapse turned out to be heterogeneous:
once a highly Ca2+-sensitive population of vesicles
was consumed, the remaining vesicles released at lower rates. These
components of release were more clearly separated in the presence of
0.5 mM EGTA, which prevented the buildup of residual
Ca2+. Conversely, raising the extracellular
Ca2+ concentration facilitated the slower population
such that its release characteristics became more similar to those of
the faster population under standard conditions. Heterogeneous release
probabilities are expected to support the maintenance of synaptic
transmission during high-frequency stimulation.
Key words:
transmitter release; synaptic depression; facilitation; release probability; vesicle pool; the calyx of Held
Copyright © 2001 Society for Neuroscience 0270-6474/01/212462-15$05.00/0
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