Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

eLife

Vincent Huson¹  Lauren Mamer²  Nils Brose³  Sebastiaan Schotten³  Lawrence Kalogreades³  Marvin Ruiter³  Marieke Meijer³  Alexander Matthias Walter³  Christian Rosenmund³  Jakob Balslev Sørensen⁴  Lennart Niels Cornelisse⁵  Matthijs Verhage⁶  Mirelle ter Veer⁶ 

[1] Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;Molecular Physiology and Cell Biology, Leibniz Institute for Molecular Pharmacology, Berlin, Germany;Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Medical Center, Amsterdam, Netherlands;Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Göttingen, Germany;Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;NeuroCure Cluster of Excellence, Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany;

关键词: synaptic strength;    fusion energy barrier;    hypertonic stimulation;    patch-clamp methodology;    mathematical modelling;    phorbol ester;   

DOI  :  10.7554/eLife.05531

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown