scholarly journals Author response: Nanodomain coupling explains Ca2+ independence of transmitter release time course at a fast central synapse

2014 ◽  
Author(s):  
Itaru Arai ◽  
Peter Jonas
Keyword(s):  
Transmitter Release ◽  
Time Course ◽  
Author Response ◽  
Release Time ◽  
Central Synapse

scholarly journals Nanodomain coupling explains Ca2+ independence of transmitter release time course at a fast central synapse

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Itaru Arai ◽  
Peter Jonas
Keyword(s):  
Purkinje Cell ◽  
Transmitter Release ◽  
Time Course ◽  
Mechanistic Explanation ◽  
Basket Cell ◽  
Release Time ◽  
Tight Coupling ◽  
Central Synapse ◽  
20 Nm ◽  
Ca2 Channels

A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release.

Single-domain/bound calcium hypothesis of transmitter release and facilitation

1996 ◽  
Vol 75 (5) ◽  
pp. 1919-1931 ◽  
Author(s):  
R. Bertram ◽  
A. Sherman ◽  
E. F. Stanley
Keyword(s):  
Transmitter Release ◽  
Time Course ◽  
Single Channel ◽  
Stimulus Frequency ◽  
Release Site ◽  
Fourth Power ◽  
Release Time ◽  
Spontaneous Release ◽  
Synaptic Dynamics ◽  
Ca2 Channels

1. We describe a model of transmitter release that is based on the finding that release can be gated during the opening of individual Ca2+ channels, suggesting that the release site can be activated by the Ca2+ domain under a single channel. In this model each release site contains four independent Ca2+ binding sites or gates with unbinding kinetics graded from slow to fast and affinities ranging from high to low. All four gates must be bound for release to occur. Thus synaptic dynamics are governed by the kinetics of Ca2+ binding and unbinding from release sites, not Ca2+ diffusion. 2. Fast facilitation occurs when an action potential invades a terminal with one or more ions remaining bound to the release sites. Residual free Ca2+ is not necessary for facilitation with this mechanism, but if present it would enhance facilitation by binding to high-affinity gates between pulses. 3. This model can account for key features of release. These include fourth-power cooperativity with regard to external Ca2+; a release time course that is virtually independent of an increase in quantal content; an inverse relation between external Ca2+ and the degree of facilitation; and a steplike increase in facilitation with increasing stimulus frequency, with each step corresponding to a unitary decline in the Ca2+ cooperativity. 4. Facilitation of single-channel-based secretion is shown to be robust even if channel opening is stochastic. Spontaneous release of transmitter, assumed to be due in part to spontaneous Ca2+ channel openings, is shown to be elevated during and after a train of impulses. 5. An extension of the model to include multiple Ca2+ channels per release site demonstrates that one role of overlapping Ca2+ domains may be to accentuate depolarization-evoked release relative to spontaneous release.

scholarly journals A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jun Guo ◽  
Jian-long Ge ◽  
Mei Hao ◽  
Zhi-cheng Sun ◽  
Xin-sheng Wu ◽  
...  
Keyword(s):  
Time Course ◽  
Current View ◽  
Vesicle Recycling ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Central Synapse ◽  
Pool Model ◽  
Underlying Mechanisms ◽  
First Time ◽  
Intense Stimulation

Abstract Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP) and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles.

Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse

Cell ◽  
1994 ◽  
Vol 79 (4) ◽  
pp. 717-727 ◽  
Author(s):  
Martin Geppert ◽  
Yukiko Goda ◽  
Robert E. Hammer ◽  
Cai Li ◽  
Thomas W. Rosahl ◽  
...  
Keyword(s):  
Transmitter Release ◽  
Synaptotagmin I ◽  
Central Synapse

scholarly journals Effect of changes in action potential shape on calcium currents and transmitter release in a calyx–type synapse of the rat auditory brainstem

1999 ◽  
Vol 354 (1381) ◽  
pp. 347-355 ◽  
Author(s):  
J. G. G. Borst ◽  
B. Sakmann
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Time Course ◽  
Calcium Influx ◽  
Auditory Brainstem ◽  
Calcium Currents ◽  
Medial Nucleus ◽  
Potential Shape ◽  
Presynaptic Calcium ◽  
Rat Brainstem

We studied the relation between the size of presynaptic calcium influx and transmitter release by making simultaneous voltage clamp recordings from presynaptic terminals, the calyces of Held and postsynaptic cells, the principal cells of the medial nucleus of the trapezoid body, in slices of the rat brainstem. Calyces were voltage clamped with different action potential waveforms. The amplitude of the excitatory postsynaptic currents depended supralinearly on the size of the calcium influx, in the absence of changes in the time–course of the calcium influx. This result is in agreement with the view thact at this synapse most vesicles are released by the combined action of multiple calcium channels.

Cholinergic agents affect two receptors that modulate transmitter release at a central synapse in Aplysia californica

1975 ◽  
Vol 88 (3) ◽  
pp. 455-474 ◽  
Author(s):  
Paul B.J. Woodson ◽  
Werner T. Schlapfer ◽  
Jacques P. Tremblay ◽  
Samuel H. Barondes
Keyword(s):  
Transmitter Release ◽  
Aplysia Californica ◽  
Central Synapse ◽  
Cholinergic Agents
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