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Presynaptic R-Type Calcium Channels Contribute to Fast Excitatory Synaptic Transmission in the Rat Hippocampus
Open accessAbstract
The possibility that R-type calcium channels contribute to fast glutamatergic transmission in the hippocampus has been assessed using low concentrations of NiCl(2) and the peptide toxin SNX 482, a selective antagonist of the pore-forming alpha(1E) subunit of R-type calcium channel. EPSPs or EPSCs were recorded in the whole-cell configuration of the patch-clamp technique mainly from CA3 hippocampal neurons. Effects of both NiCl(2) and SNX 482 were tested on large (composite) EPSCs evoked by mossy and associative-commissural fiber stimulation. NiCl(2) effects were also tested on minimal EPSPs-EPSCs. Both substances reduced the amplitude of EPSPs-EPSCs. This effect was associated with an increase in the number of response failures of minimal EPSPs-EPSCs, an enhancement of the paired-pulse facilitation ratios of both minimal and composite EPSCs, and a reduction of the inverse squared coefficient of variation (CV(-2)). The reduction of CV(-2) was positively correlated with the decrease in EPSC amplitude. The inhibitory effect of NiCl(2) was occluded by SNX 482 but not by omega-conotoxin-MVIIC, a broad-spectrum antagonist thought to interact with N- and P/Q-type calcium channels, supporting a specific action of low concentrations of NiCl(2) on R-type calcium channels. Together, these observations indicate that both NiCl(2) and SNX 482 act at presynaptic sites and block R-type calcium channels with pharmacological properties similar to those encoded by the alpha(1E) gene. These channels are involved in fast glutamatergic transmission at hippocampal synapses.
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“P/Q- (Cav2.1) and N-type Ca2+ channels (Cav2.2) are localized to active zones, and the related R-type Ca2+ channel (Cav2.3) may also be present (Gasparini et al., 2001; Li et al., 2007).”
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Metadata
- Authors
- Gasparini, S., Kasyanov, A. M., Pietrobon, D., Voronin, L. L., & Cherubini, E.
- Affiliations
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- University of Padua (IT)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-11-15
- Volume
- 21
- Issue
- 22
- Pages
- 8715-8721
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762258
- OpenAlex
- W2152544375
- Cited by
- 114
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 10
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- SDL (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Wellcome Trust
- 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 › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- R-type calcium channels, presynaptic calcium channels, hippocampus, CA3 neurons, EPSC, EPSPS, nickel chloride, SNX-482, alpha1E subunit, paired-pulse facilitation, synaptic variability, mossy fibers, omega-conotoxin MVIIC
- MeSH terms
- Animals, Calcium Channel Blockers, Hippocampus, Synaptic Transmission, Neurons, Nickel, Spider Venoms, Rats, Wistar, Presynaptic Terminals, Mossy Fibers, Hippocampal, Excitatory Postsynaptic Potentials, Calcium Channels, R-Type, Rats, In Vitro Techniques
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