Cited by 148Neuroscience and Neuropharmacology ResearchIon channel regulation and functionCellular transport and secretion

Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels

Open access
Ermolyuk, Yaroslav S, Alder, Felicity G, Surges, Rainer, Pavlov, Ivan Y, Timofeeva, Yulia, Kullmann, Dimitri M, Volynski, Kirill E·2013·Nature Neuroscience

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nn.3563

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [3]Groffen AJ Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release Science 2010 327 1614 1618 20150444 PMC2846320

Cited by

Sorted by citations

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
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review