Nakamura, Y;
Harada, H;
Kamasawa, N;
Matsui, K;
Rothman, JS;
Shigemoto, R;
Silver, RA;
... Takahashi, T; + view all
(2015)
Nanoscale distribution of presynaptic Ca(2+) channels and its impact on vesicular release during development.
Neuron
, 85
(1)
145 - 158.
10.1016/j.neuron.2014.11.019.
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Abstract
Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca(2+) channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca(2+)] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca(2+) buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca(2+) sensors for vesicular release are located at the perimeter of VGCC clusters (<30 nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.
| Type: | Article |
|---|---|
| Title: | Nanoscale distribution of presynaptic Ca(2+) channels and its impact on vesicular release during development. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuron.2014.11.019 |
| Publisher version: | http://dx.doi.org/10.1016/j.scijus.2015.01.00710.1... |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Action Potentials, Animals, Calcium, Calcium Channels, N-Type, Calcium Chelating Agents, Egtazic Acid, Exocytosis, Mice, Patch-Clamp Techniques, Presynaptic Terminals, Rats, Synapses, Synaptic Vesicles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1460649 |
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