Mobility of Calcium Channels in the Presynaptic Membrane
Open accessAbstract
Unravelling principles underlying neurotransmitter release are key to understand neural signaling. Here, we describe how surface mobility of voltage-dependent calcium channels (VDCCs) modulates release probabilities (P(r)) of synaptic vesicles (SVs). Coupling distances of 100 nm have been reported for SVs and VDCCs in different synapses. Tracking individual VDCCs revealed that within hippocampal synapses, ∼60% of VDCCs are mobile while confined to presynaptic membrane compartments. Intracellular Ca(2+) chelation decreased VDCC mobility. Increasing VDCC surface populations by co-expression of the α2δ1 subunit did not alter channel mobility but led to enlarged active zones (AZs) rather than higher channel densities. VDCCs thus scale presynaptic scaffolds to maintain local mobility. We propose that dynamic coupling based on mobile VDCCs supports calcium domain cooperativity and tunes neurotransmitter release by equalizing Pr for docked SVs within AZs.
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Observations in small CNS synapses of both clustered and random distribution of Ca2+ channels, and emerging evidence for channel mobility as an equalizer of Pr for vesicles independent of channel positioning, suggest that their precise distribution may not be the sole determinant of the active zone release likelihood landscape.
“However, observations in small CNS synapses of both clustered24,25 and random distribution of Ca2+ channels26, and emerging evidence for channel mobility as an equalizer of Pr for vesicles independent of channel positioning27 suggest that their precise distribution may not be the sole determinant of the AZ release likelihood landscape.”
From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [27]
Cites
Release probability of hippocampal glutamatergic terminals scales with the size of the active zone
Holderith, N., Lorincz, A., Katona, G., Rózsa, B., Kulik, A., Watanabe, M., & Nusser, Z. (2012) · Nature Neuroscience · doi:10.1038/nn.3137 · Cited by 405 · see citing works
Li, L., Bischofberger, J., & Jonas, P. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1709-07.2007 · Cited by 206 · see citing works
Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels
Ermolyuk, Y. S., Alder, F. G., Surges, R., Pavlov, I. Y., Timofeeva, Y., Kullmann, D. M., & Volynski, K. E. (2013) · Nature Neuroscience · doi:10.1038/nn.3563 · Cited by 148 · see citing works
Scimemi, A., & Diamond, J. S. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3827-12.2012 · Cited by 85 · see citing works
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A trans-synaptic nanocolumn aligns neurotransmitter release to receptors
Tang, A.-H., Chen, H., Li, T. P., Metzbower, S. R., MacGillavry, H. D., & Blanpied, T. A. (2016) · Nature · doi:10.1038/nature19058 · Cited by 677 · see citing works
Fukaya, R., Maglione, M., Sigrist, S. J., & Sakaba, T. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016754118 · Cited by 42 · see citing works
- Authors
- Schneider, R., Hosy, E., Kohl, J., Klueva, J., Choquet, D., Thomas, U., Voigt, A., & Heine, M.
- Affiliations
- Leibniz Institute for Neurobiology (DE)
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Corresponding author
- Heine, Martin
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 86
- Issue
- 3
- Pages
- 672-679
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2030017066
- Cited by
- 108
- References
- 4
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 15 · 2020: 11 · 2019: 9 · 2018: 14 · 2017: 10 · 2016: 8 · 2015: 5
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- 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
- voltage-gated calcium channels, channel mobility, presynaptic membrane, neurotransmitter release, release probability, synaptic vesicles, active zone, calcium chelation, α2δ-1 subunit, hippocampal synapses, docked vesicles, synaptic scaffolds
- MeSH terms
- Action Potentials, Animals, Calcium, Calcium Channel Blockers, Cells, Cultured, Chlorocebus aethiops, Embryo, Mammalian, Hippocampus, Models, Biological, Nerve Tissue Proteins, Neurons, Potassium Chloride, Synaptic Vesicles, Calcium Channels, Rats, Wistar, Presynaptic Terminals, Cadmium Chloride, Excitatory Postsynaptic Potentials, Protein Transport, Synaptotagmin I, Rats
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