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Nat Neurosci. 2013 Dec;16(12):1754-1763. doi: 10.1038/nn.3563. Epub 2013 Nov 3.

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

Author information

1
UCL Institute of Neurology, University College London, Queen Square, WC1N 3BG, United Kingdom.
2
Department of Computer Science, University of Warwick, Coventry, CV4 7AL, United Kingdom.
3
Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, United Kingdom.
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Contributed equally

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.

PMID:
24185424
PMCID:
PMC4176737
DOI:
10.1038/nn.3563
[Indexed for MEDLINE]
Free PMC Article
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