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An alien divalent ion reveals a major role for Ca²⁺ buffering in controlling slow transmitter release.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Sep 17; Vol. 34 (38), pp. 12622-35. - Publication Year :
- 2014
-
Abstract
- Ca(2+)-dependent transmitter release occurs in a fast and in a slow phase, but the differential roles of Ca(2+) buffers and Ca(2+) sensors in shaping release kinetics are still controversial. Replacing extracellular Ca(2+) by Sr(2+) causes decreased fast release but enhanced slow release at many synapses. Here, we established presynaptic Sr(2+) uncaging and made quantitative Sr(2+)- and Ca(2+)-imaging experiments at the mouse calyx of Held synapse, to reveal the interplay between Ca(2+) sensors and Ca(2+) buffers in the control of fast and slow release. We show that Sr(2+) activates the fast, Synaptotagmin-2 (Syt2) sensor for vesicle fusion with sixfold lower affinity but unchanged high cooperativity. Surprisingly, Sr(2+) also activates the slow sensor that remains in Syt2 knock-out synapses with a lower efficiency, and Sr(2+) was less efficient than Ca(2+) in the limit of low concentrations in wild-type synapses. Quantitative imaging experiments show that the buffering capacity of the nerve terminal is markedly lower for Sr(2+) than for Ca(2+) (~5-fold). This, together with an enhanced Sr(2+) permeation through presynaptic Ca(2+) channels (~2-fold), admits a drastically higher spatially averaged Sr(2+) transient compared with Ca(2+). Together, despite the lower affinity of Sr(2+) at the fast and slow sensors, the massively higher amplitudes of spatially averaged Sr(2+) transients explain the enhanced late release. This also allows us to conclude that Ca(2+) buffering normally controls late release and prevents the activation of the fast release sensor by residual Ca(2+).<br /> (Copyright © 2014 the authors 0270-6474/14/3412622-14$15.00/0.)
- Subjects :
- Animals
Chelating Agents pharmacology
Membrane Potentials drug effects
Membrane Potentials physiology
Mice
Mice, Knockout
Nerve Endings drug effects
Nerve Endings metabolism
Optical Imaging
Synaptic Transmission drug effects
Synaptotagmin II genetics
Synaptotagmin II metabolism
Calcium metabolism
Nerve Endings physiology
Strontium metabolism
Synaptic Transmission physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 34
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 25232102
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.1990-14.2014