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Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15200-5. Epub 2003 Nov 20.

The timing of phasic transmitter release is Ca2+-dependent and lacks a direct influence of presynaptic membrane potential.

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1
AG Synaptische Dynamik und Modulation and Abteilung Membranbiophysik, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, D-37077 Göttingen, Germany.

Abstract

Ca2+ influx through voltage-gated Ca2+ channels and the resulting elevation of intracellular Ca2+ concentration, [Ca2+]i, triggers transmitter release in nerve terminals. However, it is controversial whether in addition to the opening of Ca2+ channels, membrane potential directly affects transmitter release. Here, we assayed the influence of membrane potential on transmitter release at the calyx of Held nerve terminals. Transmitter release was evoked by presynaptic Ca2+ uncaging, or by presynaptic Ca2+ uncaging paired with presynaptic voltage-clamp depolarizations to +80 mV, under pharmacological block of voltage-gated Ca2+ channels. Such a change in membrane potential did not alter the Ca2+ dependence of transmitter release rates or synaptic delays. We also found, by varying the amount of Ca2+ influx during Ca2+ tail-currents, that the time course of phasic transmitter release is not invariant to changes in release probability. Rather, the time difference between peak Ca2+ current and peak transmitter release became progressively shorter with increasing Ca2+ current amplitude. When this time difference was plotted as a function of the estimated local [Ca2+]i at the sites of vesicle fusion, a slope of approximately 100 micros per 10 microM [Ca2+]i was found, in reasonable agreement with a model of cooperative Ca2+ binding and vesicle fusion. Thus, the amplitude and time course of the [Ca2+]i signal at the sites of vesicle fusion controls the timing and the amount of transmitter release, both under conditions of brief periods of Ca2+ influx, as well as during step-like elevations of [Ca2+]i produced by Ca2+ uncaging.

PMID:
14630950
PMCID:
PMC299956
DOI:
10.1073/pnas.2433276100
[Indexed for MEDLINE]
Free PMC Article
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