title: Transmitter release is evoked with low probability predominately by calcium flux through single channel openings at the frog neuromuscular junction.
abstract: The quantitative relationship between presynaptic calcium influx and transmitter release critically depends on the spatial coupling of presynaptic calcium channels to synaptic vesicles. When there is a close association between calcium channels and synaptic vesicles, the flux through a single open calcium channel may be sufficient to trigger transmitter release. With increasing spatial distance, however, a larger number of open calcium channels might be required to contribute sufficient calcium ions to trigger vesicle fusion. Here we used a combination of pharmacological calcium channel block, high-resolution calcium imaging, postsynaptic recording, and 3D Monte Carlo reaction-diffusion simulations in the adult frog neuromuscular junction, to show that release of individual synaptic vesicles is predominately triggered by calcium ions entering the nerve terminal through the nearest open calcium channel. Furthermore, calcium ion flux through this channel has a low probability of triggering synaptic vesicle fusion (∼6%), even when multiple channels open in a single active zone. These mechanisms work to control the rare triggering of vesicle fusion in the frog neuromuscular junction from each of the tens of thousands of individual release sites at this large model synapse.
authors: Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for the Neural Basis of Cognition, Pittsburgh, Pennsylvania;
authors: Fujun
authors: F
authors: Luo
authors: Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Biomedical Applications Group, Pittsburgh Supercomputing Center, Carnegie Mellon University, Pittsburgh, Pennsylvania; and Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Markus
authors: M
authors: Dittrich
authors: Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors: Soyoun
authors: S
authors: Cho
authors: Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Biomedical Applications Group, Pittsburgh Supercomputing Center, Carnegie Mellon University, Pittsburgh, Pennsylvania; and Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Joel R
authors: JR
authors: Stiles
authors: Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for the Neural Basis of Cognition, Pittsburgh, Pennsylvania; meriney@pitt.edu.
authors: Stephen D
authors: SD
authors: Meriney
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling; D009010:Monte Carlo Method; D009469:Neuromuscular Junction / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology; D011894:Rana pipiens; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology
chemical_list: D015220:Calcium Channels
keywords: MCell; active zone; calcium channels; neuromuscular junction; synapse
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