Nanodomain Coupling between Ca2+ Channels and Ca2+ Sensors Promotes Fast and Efficient Transmitter Release at a Cortical GABAergic Synapse
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It is generally thought that transmitter release at mammalian central synapses is triggered by Ca2+ microdomains, implying loose coupling between presynaptic Ca2+ channels and Ca2+ sensors of exocytosis. Here we show that Ca2+ channel subunit immunoreactivity is highly concentrated in the active zone of GABAergic presynaptic terminals of putative parvalbumin-containing basket cells in the hippocampus. Paired recording combined with presynaptic patch pipette perfusion revealed that GABA release at basket cell-granule cell synapses is sensitive to millimolar concentrations of the fast Ca2+ chelator BAPTA but insensitive to the slow Ca2+ chelator EGTA. These results show that Ca2+ source and Ca2+ sensor are tightly coupled at this synapse, with distances in the range of 10-20 nm. Models of Ca2+ inflow-exocytosis coupling further reveal that the tightness of coupling increases efficacy, speed, and temporal precision of transmitter release. Thus, tight coupling contributes to fast feedforward and feedback inhibition in the hippocampal network.
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Modeling of Ca2+ domains showed that tightening of coupling increases Pr approximately 10-fold per 20 nm change in coupling distance.
“Modeling of Ca2+ domains showed that tightening of coupling increases Pr approximately 10-fold per 20 nm change in coupling distance [87,88].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [87]
The short physical distance between the site of Ca2+ entry and the synaptic release machinery enforces a tight coupling between action potential invasion and neurotransmitter release with rapid and precise temporal dynamics.
“The short physical distance between the site of Ca2+ entry and the synaptic release machinery enforces a tight coupling between action potential invasion and neurotransmitter release with rapid and precise temporal dynamics (132, 477).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [132]
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- Authors
- Bucurenciu, I., Kulik, A., Schwaller, B., Frotscher, M., & Jonas, P.
- Affiliations
- University of Freiburg (DE)
- University of Fribourg (CH)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 57
- Issue
- 4
- Pages
- 536-545
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2033866317
- Cited by
- 274
- References
- 51
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 12 · 2023: 13 · 2022: 14 · 2021: 11 · 2020: 7 · 2019: 14 · 2018: 21 · 2017: 16 · 2016: 10 · 2015: 19 · 2014: 24 · 2013: 12 · 2012: 20
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- calcium microdomains, GABAergic synapses, basket cells, parvalbumin, active zone, exocytosis, neurotransmitter release, BAPTA, EGTA, calcium chelation, hippocampus, granule cells, feedforward inhibition, product inhibition
- MeSH terms
- Animals, gamma-Aminobutyric Acid, Hippocampus, Synaptic Transmission, Synapses, Calcium Channels, Rats, Wistar, Calcium Signaling, Nanotechnology, Rats
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