Voltage‐gated calcium channel nanodomains: molecular composition and function
Abstract
Voltage‐gated calcium (Ca V) channels and their regulation by proteins at the synaptic cleft play a critical role in neurotransmission. These interactions fine‐tune the synaptic response through the regulation of Ca 2+ entry into the presynaptic terminal and trigger the fusion of vesicles filled with neurotransmitters and peptides. Regulation of Ca V channel intrinsic properties and their numbers at the active zones shape the timing and strength of synaptic function. Here, we provide an overview of a number of proteins reported to be part of Ca V channel nanodomains at the synaptic cleft and the repercussions of these interactions for Ca V channel trafficking, tethering at the active zone, and regulation of their biophysical properties. We summarize the current state of knowledge by which Ca V channels are regulated at presynaptic sites.
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The alpha-1 subunit of CaV channels is the pore-forming subunit and has a fundamental role in the selective gating and regulated entry of calcium ions into cells.
“The alpha-1 subunit of CaV channels is the pore-forming subunit and has a fundamental role in the selective gating and regulated entry of calcium ions into cells55,56.”
From CYFIP1 governs the development of cortical axons by modulating calcium availability (2025) · cites this paper as [56]
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References 170 · Cited by 44
- Authors
- Gandini, M. A., & Zamponi, G. W.
- Affiliations
- Department of Physiology and Pharmacology Alberta Children’s Hospital Research Institute Hotchkiss Brain Institute Cumming School of Medicine University of Calgary AB Canada
- University of Calgary (CA)
- Corresponding author
- Zamponi, Gerald W.
- ORCID
- Zamponi, Gerald W.
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2021-02-25
- Volume
- 289
- Issue
- 3
- Pages
- 614-633
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W3126631836
- Cited by
- 44
- References
- 170
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 14 · 2023: 10 · 2022: 9 · 2021: 3
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- voltage-gated calcium channels, synaptic cleft, presynaptic terminals, active zone, nanodomains, synaptic vesicle fusion, neurotransmitter release, channel trafficking, channel regulation, synaptic transmission
- MeSH terms
- Calcium, Calcium-Binding Proteins, Humans, Synaptic Transmission, Neurons, Synapses, Calcium Channels, Presynaptic Terminals, Calcium Signaling
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