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An Alien Divalent Ion Reveals a Major Role for Ca2+ Buffering in Controlling Slow Transmitter Release
- Source :
- Journal of Neuroscience. 34:12622-12635
- Publication Year :
- 2014
- Publisher :
- Society for Neuroscience, 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+).
- Subjects :
- inorganic chemicals
slow release sensor
chemistry.chemical_classification
0303 health sciences
Vesicle fusion
General Neuroscience
Kinetics
endogenous fixed buffer
Cooperativity
calcium buffering capacity
Synaptotagmin 1
Divalent
Synapse
synaptotagmin
03 medical and health sciences
0302 clinical medicine
chemistry
Biophysics
Extracellular
calcium sensor
strontium
Calyx of Held
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....cc3a28d0f4669a232568c7cb5cfd5b62