Miniature endplate current rise times <100 mu s from improved dual recordings can be modeled with passive acetylcholine diffusion from a synaptic vesicle

We recorded miniature endplate currents (mEPCs) using simultaneous voltage clamp and extracellular methods, allowing correction for time course measurement errors, We obtained a 20-80% rise time (t(r)) of approximate to 80 mu s at 22 degrees C, shorter than any previously reported values, and t(r) variability (SD) with an upper limit of 25-30 mu s. Extracellular electrode pressure can increase t(r) and its variability by 2- to 3-fold, Using Monte Carlo simulations, we modeled passive acetylcholine diffusion through a vesicle fusion pore expanding radially at 25 nm . ms(-1) (rapid, from endplate Omega figure appearance) or 0.275 nm . ms(-1) (slow, from mast cell exocytosis), Simulated mEPCs obtained with rapid expansion reproduced t(r) and the overall shape of our experimental mEPCs, and were similar to simulated mEPCs obtained with instant acetylcholine release, We conclude that passive transmitter diffusion, coupled with rapid expansion of the fusion pore, is sufficient to explain the time course of experimentally measured synaptic currents with t(r)s of less than 100 mu s.