The Yin and Yang of Calcium Effects on Synaptic Vesicle Endocytosis
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A large number of studies suggest that calcium triggers and accelerates vesicle endocytosis at many synapses and non-neuronal secretory cells. However, many studies show that prolonging the duration of the stimulation train, which induces more calcium influx, slows down endocytosis; and several studies suggest that instead of triggering endocytosis, calcium actually inhibits endocytosis. Here we addressed this apparent conflict at a large nerve terminal, the calyx of Held in rat brainstem, in which recent studies suggest that transient calcium increase up to tens of micromolar concentration at the micro/nano domain triggers endocytosis. By dialyzing 0–1 μ m calcium into the calyx via a whole-cell pipette, we found that slow endocytosis was inhibited by calcium dialysis in a concentration-dependent manner. Thus, prolonged, small, and global calcium increase inhibits endocytosis, whereas transient and large calcium increase at the micro/nano domain triggers endocytosis and facilitates endocytosis. This yin and yang effect of calcium may reconcile apparent conflicts regarding whether calcium accelerates or inhibits endocytosis. Whether endocytosis is fast or slow depends on the net outcome between the yin and yang effect of calcium.
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Several previous studies suggest that endocytosis becomes slower when neurons are treated with the high-affinity calcium chelator EGTA, which abolishes asynchronous release.
“Consistent with this notion, several previous studies suggest that endocytosis becomes slower when neurons are treated with the high-affinity calcium chelator EGTA, which abolishes asynchronous release77–81.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [80]
The Introduction (page unavailable) says that studies found calcium buffering with EGTA slows endocytosis at many synapses. The section “Prolonged calcium concentration increase inhibits slow endocytosis” (page unavailable) says EGTA should prevent residual calcium from generating large amounts of asynchronous release, but does not say it abolishes asynchronous release. (LLM, conf=0.87)
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Cited by
Sorted by citations
Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis
Ogunmowo, T. H., Jing, H., Raychaudhuri, S., Kusick, G. F., Imoto, Y., Li, S., Itoh, K., Ma, Y., Jafri, H., Dalva, M. B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38595-2 · Cited by 51 · see citing works
- Authors
- Wu, X.-S., & Wu, L.-G.
- Affiliations
- National Institute of Neurological Disorders and Stroke (US)
- ORCID
- Wu, Ling-Gang
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-02-12
- Volume
- 34
- Issue
- 7
- Pages
- 2652-2659
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3921431
- OpenAlex
- W2011735549
- Cited by
- 41
- References
- 0
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 5
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- calcium, synaptic vesicle endocytosis, calyx of Held, calcium influx, endocytosis inhibition, presynaptic terminals, neurotransmitter release
- MeSH terms
- Animals, Brain Stem, Calcium, Endocytosis, Organ Culture Techniques, Synaptic Vesicles, Patch-Clamp Techniques, Rats
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