Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate
- VU University Medical Center, Netherlands
- Charité, Universitätsmedizin Berlin, Germany
- Max Planck Institute for Experimental Medicine, Germany
- University of Copenhagen, Denmark
Abstract
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 versus 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.
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© 2015, Schotten et al.
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Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate
eLife 4:e05531.
https://doi.org/10.7554/eLife.05531
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