Journal
JOURNAL OF NEUROPHYSIOLOGY
Volume 113, Issue 7, Pages 2480-2489Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00879.2014
Keywords
neuromuscular junction; calcium channels; active zone; synapse; MCell
Categories
Funding
- National Institutes of Health [R01-NS-043396, R01-NS090644, R01-GM-068630, P41-RR-06009, P41-GM-103712]
- National Science Foundation [0844174, 0844604, 1249546]
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [0844174] Funding Source: National Science Foundation
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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 (similar to 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.
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