Miniature Endplate Current Rise Times <100 μ s from Improved Dual Recordings Can be Modeled with Passive Acetylcholine Diffusion from a Synaptic Vesicle

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-06, Vol.93 (12), p.5747-5752
• Main Authors: Stiles, Joel R., Van Helden, Dirk, Bartol, Thomas M., Salpeter, Edwin E., Salpeter, Miriam M.
• Format: Article
• Language: English
• Subjects: Anolis carolinensis; Biophysics; Cholinergic receptors; Electric current; Electric potential; Electrodes; Mast cells; Modeling; Neurobiology; Neurons; Porosity
• ISSN: 0027-8424
• DOI: 10.1073/pnas.93.12.5747

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 (tr) of ≈ 80 μ s at 22 degrees C, shorter than any previously reported values, and tr variability (SD) with an upper limit of 25-30 μ s. Extracellular electrode pressure can increase tr 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 Ω figure appearance) or 0.275 nm· ms-1 (slow, from mast cell exocytosis). Simulated mEPCs obtained with rapid expansion reproduced tr 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 trs of less than 100 μ s.