title: Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels.
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.
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, WC1N 3BG, United Kingdom.
authors.forename: Yaroslav S
authors.initials: YS
authors.lastname: Ermolyuk
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, WC1N 3BG, United Kingdom.
authors.forename: Felicity G
authors.initials: FG
authors.lastname: Alder
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, WC1N 3BG, United Kingdom.
authors.forename: Rainer
authors.initials: R
authors.lastname: Surges
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, WC1N 3BG, United Kingdom.
authors.forename: Ivan Y
authors.initials: IY
authors.lastname: Pavlov
authors.affiliation: Department of Computer Science, University of Warwick, Coventry, CV4 7AL, United Kingdom.|Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, United Kingdom.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Timofeeva
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, WC1N 3BG, United Kingdom.
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Kullmann
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, WC1N 3BG, United Kingdom.
authors.forename: Kirill E
authors.initials: KE
authors.lastname: Volynski
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000145:classification* / Q000502:physiology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013269:Stochastic Processes
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D018698:Glutamic Acid; D004533:Egtazic Acid; C046770:EGTA acetoxymethyl ester; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium