ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
An alien divalent ion reveals a major role for Ca²⁺ buffering in controlling slow transmitter release.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Synaptotagmins 3 and 7 mediate the majority of asynchronous release from synapses in the cerebellum and hippocampus.Cell reports · 2024Article
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- Studying Synaptic Connectivity and Strength with Optogenetics and Patch-Clamp Electrophysiology.International journal of molecular sciences · 2022Review
- Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Synaptotagmin 7 Mediates Both Facilitation and Asynchronous Release at Granule Cell Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Dynamics of volume-averaged intracellular CaThe Journal of physiology · 2017Article
- Parallel processing of afferent olfactory sensory information.The Journal of physiology · 2016Article
- Desensitization-resistant and -sensitive GPCR-mediated inhibition of GABA release occurs by Ca2+-dependent and -independent mechanisms at a hypothalamic synapse.Journal of neurophysiology · 2016Article
- Molecular Machines Regulating the Release Probability of Synaptic Vesicles at the Active Zone.Frontiers in synaptic neuroscience · 2016Review
- An Engineered Metal Sensor Tunes the Kinetics of Synaptic Transmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Molecular mechanisms governing Ca(2+) regulation of evoked and spontaneous release.Nature neuroscience · 2015Review
- Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release Control by Multiple Channels at a CNS Synapse.PLoS computational biology · 2015Article
- Ca2+ channel to synaptic vesicle distance accounts for the readily releasable pool kinetics at a functionally mature auditory synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
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4 authors.
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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+).
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