In a model of exocytosis, alcohol enhances vesicle fusion by acting on membrane lipids, not SNARE proteins.

Abstract

Many studies have shown that alcohol can affect release of neurotransmitter from neurons through pre- and post-synaptic mechanisms. Fewer studies have focused on alcohol's direct effect on fusion of synaptic vesicles, the final step before neurotransmitter release. We tested whether methanol and ethanol affect SNARE driven fusion in a model system of neurotransmitter release. We then identified what parts of our simplified system were specifically affected. Our results show that ethanol is more potent than methanol at increasing fusion probability. The ethanol enhancement is significant at doses that are in the physiologically relevant range. Three different methods showed that alcohol had no effect on SNARE proteins until ≥10x higher concentrations. Another model of exocytosis, without SNARE proteins (i.e. only lipid membranes), showed an increase in fusion rates under the same conditions. These results provide strong evidence that ethanol alters lipid membranes to enhance fusion in our model of exocytosis.