ArticleBiophysical journal2013
An excess-calcium-binding-site model predicts neurotransmitter release at the neuromuscular junction.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Trans-synaptic molecular context of NMDA receptor nanodomains.Nature communications · 2025Article
- Dynamic regulation of vesicle pools in a detailed spatial model of the complete synaptic vesicle cycle.Science advances · 2025Article
- Vesicle and reaction-diffusion hybrid modeling with STEPS.Communications biology · 2024Article
- Simulations of active zone structure and function at mammalian NMJs predict that loss of calcium channels alone is not sufficient to replicate LEMS effects.Journal of neurophysiology · 2023Article
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- Article
- Neuromuscular Active Zone Structure and Function in Healthy and Lambert-Eaton Myasthenic Syndrome States.Biomolecules · 2022Review
- Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites.Frontiers in synaptic neuroscience · 2022Review
- A first-passage approach to diffusion-influenced reversible binding and its insights into nanoscale signaling at the presynapse.Scientific reports · 2021Article
- Hypothesis Relating the Structure, Biochemistry and Function of Active Zone Material Macromolecules at a Neuromuscular Junction.Frontiers in synaptic neuroscience · 2021Article
- Dynamics of Neuromuscular Transmission Reproduced by Calcium-Dependent and Reversible Serial Transitions in the Vesicle Fusion Complex.Frontiers in synaptic neuroscience · 2021Article
- The Frog Motor Nerve Terminal Has Very Brief Action Potentials and Three Electrical Regions Predicted to Differentially Control Transmitter Release.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- The control of release probability at nerve terminals.Nature reviews. Neuroscience · 2019Review
- Presynaptic mechanisms controlling calcium-triggered transmitter release at the neuromuscular junction.Current opinion in physiology · 2018Article
- Transmitter release site organization can predict synaptic function at the neuromuscular junction.Journal of neurophysiology · 2018Article
- Impact of spatiotemporal calcium dynamics within presynaptic active zones on synaptic delay at the frog neuromuscular junction.Journal of neurophysiology · 2018Article
- The First 100 nm Inside the Pre-synaptic Terminal Where Calcium Diffusion Triggers Vesicular Release.Frontiers in synaptic neuroscience · 2018Review
- The Calcium Channel C-Terminal and Synaptic Vesicle Tethering: Analysis by Immuno-Nanogold Localization.Frontiers in cellular neuroscience · 2017Article
- Hybrid Markov-mass action law model for cell activation by rare binding events: Application to calcium induced vesicular release at neuronal synapses.Scientific reports · 2016Article
- Unbiased Rare Event Sampling in Spatial Stochastic Systems Biology Models Using a Weighted Ensemble of Trajectories.PLoS computational biology · 2016Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Despite decades of intense experimental studies, we still lack a detailed understanding of synaptic function. Fortunately, using computational approaches, we can obtain important new insights into the inner workings of these important neural systems. Here, we report the development of a spatially realistic computational model of an entire frog active zone in which we constrained model parameters with experimental data, and then used Monte Carlo simulation methods to predict the Ca(2+)-binding stoichiometry and dynamics that underlie neurotransmitter release. Our model reveals that 20-40 independent Ca(2+)-binding sites on synaptic vesicles, only a fraction of which need to bind Ca(2+) to trigger fusion, are sufficient to predict physiological release. Our excess-Ca(2+)-binding-site model has many functional advantages, agrees with recent data on synaptotagmin copy number, and is the first (to our knowledge) to link detailed physiological observations with the molecular machinery of Ca(2+)-triggered exocytosis. In addition, our model provides detailed microscopic insight into the underlying Ca(2+) dynamics during synapse activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.