High-Speed Imaging Reveals the Bimodal Nature of Dense Core Vesicle Exocytosis and Jet Flow through the Fusion Pore

Abstract

ABSTRACTDuring exocytosis, the fusion of secretory vesicle with plasma membrane forms a pore that regulates release of neurotransmitter and peptide. Osmotic forces contribute to exocytosis but release through the pore is thought to occur by diffusion. Heterogeneity of fusion pore behavior has also suggested stochastic variation in a common exocytic mechanism, implying a lack of biological control. Imaging at millisecond resolution to observe the first events in exocytosis, we find that fusion pore duration is bimodal rather than stochastic. Loss of calcium sensor synaptotagmin 7 increases the proportion of slow events without changing the intrinsic properties of either class, indicating the potential for independent regulation. In addition, dual imaging shows a delay in the entry of external dye relative to release that indicates discharge at high velocity rather than strictly by diffusion.