An excess-calcium-binding-site model predicts neurotransmitter release at the neuromuscular junction

Markus Dittrich, John M. Pattillo, J. Darwin King, Soyoun Cho, Joel R. Stiles, Stephen D. Meriney

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 Ca2+-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 Ca2+ to trigger fusion, are sufficient to predict physiological release. Our excess-Ca2+-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 Ca2+-triggered exocytosis. In addition, our model provides detailed microscopic insight into the underlying Ca2+ dynamics during synapse activation.

Original languageEnglish (US)
Pages (from-to)2751-2763
Number of pages13
JournalBiophysical journal
Volume104
Issue number12
DOIs
StatePublished - Jun 18 2013

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Neuromuscular Junction
Neurotransmitter Agents
Binding Sites
Synaptotagmins
Calcium
Monte Carlo Method
Synaptic Vesicles
Exocytosis
Anura
Synapses

ASJC Scopus subject areas

  • Biophysics

Cite this

An excess-calcium-binding-site model predicts neurotransmitter release at the neuromuscular junction. / Dittrich, Markus; Pattillo, John M.; King, J. Darwin; Cho, Soyoun; Stiles, Joel R.; Meriney, Stephen D.

In: Biophysical journal, Vol. 104, No. 12, 18.06.2013, p. 2751-2763.

Research output: Contribution to journalArticle

Dittrich, Markus ; Pattillo, John M. ; King, J. Darwin ; Cho, Soyoun ; Stiles, Joel R. ; Meriney, Stephen D. / An excess-calcium-binding-site model predicts neurotransmitter release at the neuromuscular junction. In: Biophysical journal. 2013 ; Vol. 104, No. 12. pp. 2751-2763.
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