Transmitter release is evoked with low probability predominately by calcium flux through single channel openings at the frog neuromuscular junction

Fujun Luo, Markus Dittrich, Soyoun Cho, Joel R. Stiles, Stephen D. Meriney

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2480-2489
Number of pages10
JournalJournal of Neurophysiology
Volume113
Issue number7
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Neuromuscular Junction
Calcium Channels
Anura
Synaptic Vesicles
Calcium
Ions
Synapses
Pharmacology

Keywords

  • Active zone
  • Calcium channels
  • MCell
  • Neuromuscular junction
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Transmitter release is evoked with low probability predominately by calcium flux through single channel openings at the frog neuromuscular junction. / Luo, Fujun; Dittrich, Markus; Cho, Soyoun; Stiles, Joel R.; Meriney, Stephen D.

In: Journal of Neurophysiology, Vol. 113, No. 7, 01.04.2015, p. 2480-2489.

Research output: Contribution to journalArticle

@article{c3c35240fa024131b9172175aee821d4,
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.",
keywords = "Active zone, Calcium channels, MCell, Neuromuscular junction, Synapse",
author = "Fujun Luo and Markus Dittrich and Soyoun Cho and Stiles, {Joel R.} and Meriney, {Stephen D.}",
year = "2015",
month = "4",
day = "1",
doi = "10.1152/jn.00879.2014",
language = "English (US)",
volume = "113",
pages = "2480--2489",
journal = "Journal of Neurophysiology",
issn = "0022-3077",
publisher = "American Physiological Society",
number = "7",

}

TY - JOUR

T1 - Transmitter release is evoked with low probability predominately by calcium flux through single channel openings at the frog neuromuscular junction

AU - Luo, Fujun

AU - Dittrich, Markus

AU - Cho, Soyoun

AU - Stiles, Joel R.

AU - Meriney, Stephen D.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

KW - Active zone

KW - Calcium channels

KW - MCell

KW - Neuromuscular junction

KW - Synapse

UR - http://www.scopus.com/inward/record.url?scp=84979852070&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979852070&partnerID=8YFLogxK

U2 - 10.1152/jn.00879.2014

DO - 10.1152/jn.00879.2014

M3 - Article

VL - 113

SP - 2480

EP - 2489

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

IS - 7

ER -