期刊
ELIFE
卷 4, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.05531
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资金
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek CLS project [635100020]
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek Complexity project [645.000.003, 645000003]
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek TOP project [91207032]
- Fourth Framework Programme (European Union Fourth Framework Programme) Synsys [Health-F4-2010-242167]
- Fourth Framework Programme (European Union Fourth Framework Programme) Eurospin [Health-F2-2009-241498]
- European Commission Second Framework Programme: Eurospin [Health-F2-2009-241498]
- Lundbeck Foundation [R183-2014-3274, R28-2008-1976] Funding Source: researchfish
- Novo Nordisk Fonden [NNF14OC0012557] Funding Source: researchfish
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.
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