Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels
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The role of voltage-gated Ca2+ channels (VGCCs) in spontaneous miniature neurotransmitter release is incompletely understood. We found that stochastic opening of P/Q-, N- and R-type VGCCs accounts for ∼50% of all spontaneous glutamate release at rat cultured hippocampal synapses, and that R-type channels have a far greater role in spontaneous than in action potential-evoked exocytosis. VGCC-dependent miniature neurotransmitter release (minis) showed similar sensitivity to presynaptic Ca2+ chelation as evoked release, arguing for direct triggering of spontaneous release by transient spatially localized Ca(2+) domains. Experimentally constrained three-dimensional diffusion modeling of Ca2+ influx-exocytosis coupling was consistent with clustered distribution of VGCCs in the active zone of small hippocampal synapses and revealed that spontaneous VGCCs openings can account for the experimentally observed VGCC-dependent minis, although single channel openings triggered release with low probability. Uncorrelated stochastic VGCC opening is therefore a major trigger for spontaneous glutamate release, with differential roles for distinct channel subtypes.
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Evoked Pr is significantly positively correlated with Syn1a area.
“evoked Pr was significantly positively correlated with Syn1a area, as reported previously50”
From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [50]
The Results section on modeling action potential-evoked release reports vesicular fusion probabilities for different channel-distribution models, but not a correlation with Syn1a area. Searches for “Syn1a,” synapsin area, and evoked release probability versus bouton area found no passage reporting the claimed correlation. Page numbers were unavailable in our copy. (LLM, conf=0.72)
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- Authors
- Ermolyuk, Y. S., Alder, F. G., Surges, R., Pavlov, I. Y., Timofeeva, Y., Kullmann, D. M., & Volynski, K. E.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- University of Warwick (GB)
- Corresponding author
- Volynski, Kirill E
- Venue
- Nature Neuroscience
- Published
- 2013-11-03
- Volume
- 16
- Issue
- 12
- Pages
- 1754-1763
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4176737
- OpenAlex
- W2056943012
- Cited by
- 148
- References
- 60
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 6 · 2023: 14 · 2022: 12 · 2021: 9 · 2020: 14 · 2019: 11 · 2018: 15 · 2017: 17 · 2016: 9 · 2015: 18 · 2014: 8
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (095580)
- Action Medical Research
- Home Office
- Medical Research Council (MR/K000608/1)
- Biotechnology and Biological Sciences Research Council (BB/H011900/1)
- 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
- spontaneous glutamate release, voltage-gated calcium channels, P/Q-type calcium channels, N-type calcium channels, R-type calcium channels, calcium nanodomains, hippocampal synapses, active zone
- MeSH terms
- Animals, Animals, Newborn, Calcium, Calcium Channel Agonists, Calcium Channel Blockers, Cells, Cultured, Chelating Agents, Egtazic Acid, Electric Stimulation, Hippocampus, Models, Biological, Neurons, Stochastic Processes, Calcium Channels, Ion Channel Gating, Rats, Sprague-Dawley, Patch-Clamp Techniques, Glutamic Acid, Excitatory Postsynaptic Potentials, Rats
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