Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
The energy required to fuse synaptic vesicles with the plasma membrane (‘activation energy’) is considered a major determinant in synaptic efficacy. From reaction rate theory, we predict that a class of modulations exists, which utilize linear modulation of the energy barrier for fusion to achieve supralinear effects on the fusion rate. To test this prediction experimentally, we developed a method to assess the number of releasable vesicles, rate constants for vesicle priming, unpriming, and fusion, and the activation energy for fusion by fitting a vesicle state model to synaptic responses induced by hypertonic solutions. We show that complexinI/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive vs multiplicative relationship between activation energy and fusion rate provides a novel explanation for previously observed non-linear effects of genetic/pharmacological perturbations on synaptic transmission and a novel interpretation of the cooperative nature of Ca2+-dependent release.
Originalsprog | Engelsk |
---|---|
Artikelnummer | e05531 |
Tidsskrift | eLife |
Vol/bind | 4 |
Sider (fra-til) | 1-25 |
Antal sider | 25 |
ISSN | 2050-084X |
DOI | |
Status | Udgivet - 2015 |
ID: 137165356