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Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation

Timofeeva, Y; Volynski, KE; (2015) Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation. Frontiers in Cellular Neuroscience , 9 , Article 239. 10.3389/fncel.2015.00239. Green open access

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Abstract

Action potential-dependent release of synaptic vesicles and short-term synaptic plasticity are dynamically regulated by the endogenous Ca(2+) buffers that shape [Ca(2+)] profiles within a presynaptic bouton. Calmodulin is one of the most abundant presynaptic proteins and it binds Ca(2+) faster than any other characterized endogenous neuronal Ca(2+) buffer. Direct effects of calmodulin on fast presynaptic Ca(2+) dynamics and vesicular release however have not been studied in detail. Using experimentally constrained three-dimensional diffusion modeling of Ca(2+) influx-exocytosis coupling at small excitatory synapses we show that, at physiologically relevant concentrations, Ca(2+) buffering by calmodulin plays a dominant role in inhibiting vesicular release and in modulating short-term synaptic plasticity. We also propose a novel and potentially powerful mechanism for short-term facilitation based on Ca(2+)-dependent dynamic dislocation of calmodulin molecules from the plasma membrane within the active zone.

Type: Article
Title: Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fncel.2015.00239
Publisher version: http://dx.doi.org/10.3389/fncel.2015.00239
Language: English
Additional information: © 2015 Timofeeva and Volynski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: calcium channels, modeling biological systems, short-term plasticity, synaptic transmission, synaptic vesicles
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/1472598
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