Figure 8.
Simulation of FALI-mediated tether disruption. A, Schematic of simulations. During simulations of FALI (represented as a light bulb), all attached vesicles and 25% of primed vesicles (gray in schematic) were prohibited from moving along the side of the ribbon. In addition, the affected primed vesicles were unable to be released, removing them from the RRP but not the base of the ribbon. B, Voltage step protocol for simulations, with a holding Vm = −60 mV followed by a 100 ms step to −10 mV every 10 s. Immediately before the onset of the second step, FALI-mediated tether disruption was simulated (dashed inset). C, The number of vesicles released (during 5 ms bins) as a function of simulation time. Trace is an average of 53 simulations. Inset, Comparison of responses to Vm step (to −10 mV), colors corresponding to steps indicated by asterisks. D, The changes in vesicle pools at the base of the ribbon that occurred during the simulation. Although the simulated FALI only immobilized 25% of primed vesicles, the primed pool only recovered to ∼5 vesicles. Alternatively, the total number of vesicles at the base of the ribbon (i.e., those either docked or frozen by FALI) was not substantially reduced. Primed trace represents the average of 53 simulations. Docked or frozen trace represents the average of 35 simulations.