Synaptotagmin modulation of fusion pore kinetics in regulated exocytosis of dense-core vesicles

In the exocytosis of neurotransmitter, fusion pore opening represents the f irst instant of fluid contact between the vesicle lumen and extracellular s pace. The existence of the fusion pore has been established by electrical m easurements, but its molecular composition is unknown. The possibility that synaptotagmin regulates fusion pores was investigated with amperometry to monitor exocytosis of single dense-core vesicles. Overexpression of synapto tagmin I prolonged the time from fusion pore opening to dilation, whereas s ynaptotagmin IV shortened this time. Both synaptotagmin isoforms reduced no repinephrine flux through open fusion pores. Thus, synaptotagmin interacts with fusion pores, possibly by associating with a core complex of membrane proteins and/or lipid.