title: Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation.
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.
authors.affiliation: Department of Computer Science, University of Warwick Coventry, UK ; Centre for Complexity Science, University of Warwick Coventry, UK.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Timofeeva
authors.affiliation: University College London Institute of Neurology, University College London London, UK.
authors.forename: Kirill E
authors.initials: KE
authors.lastname: Volynski
keywords: calcium channels; modeling biological systems; short-term plasticity; synaptic transmission; synaptic vesicles