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© MPI f. Dynamik und Selbstorganisation
Publication : Scientific reports

A first-passage approach to diffusion-influenced reversible binding and its insights into nanoscale signaling at the presynapse.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Scientific reports - 08 Mar 2021

Reva M, DiGregorio DA, Grebenkov DS,

Link to Pubmed [PMID] – 33686123

Link to DOI – 10.1038/s41598-021-84340-4

Sci Rep 2021 Mar; 11(1): 5377

Synaptic transmission between neurons is governed by a cascade of stochastic calcium ion reaction-diffusion events within nerve terminals leading to vesicular release of neurotransmitter. Since experimental measurements of such systems are challenging due to their nanometer and sub-millisecond scale, numerical simulations remain the principal tool for studying calcium-dependent neurotransmitter release driven by electrical impulses, despite the limitations of time-consuming calculations. In this paper, we develop an analytical solution to rapidly explore dynamical stochastic reaction-diffusion problems based on first-passage times. This is the first analytical model that accounts simultaneously for relevant statistical features of calcium ion diffusion, buffering, and its binding/unbinding reaction with a calcium sensor for synaptic vesicle fusion. In particular, unbinding kinetics are shown to have a major impact on submillisecond sensor occupancy probability and therefore cannot be neglected. Using Monte Carlo simulations we validated our analytical solution for instantaneous calcium influx and that through voltage-gated calcium channels. We present a fast and rigorous analytical tool that permits a systematic exploration of the influence of various biophysical parameters on molecular interactions within cells, and which can serve as a building block for more general cell signaling simulators.

https://pubmed.ncbi.nlm.nih.gov/33686123