Facilitation is an important form of short-term plasticity that occurs in m
ost synapses. At crayfish neuromuscular junctions, basal transmission and f
acilitation were significantly reduced after presynaptic introduction of "f
ast" high-affinity calcium buffers, and the decay of facilitation was accel
erated. The existence of residual calcium during facilitation was also demo
nstrated. Computational modeling of three-dimensional buffered Ca2+ diffusi
on and binding to secretory and facilitation targets suggest that the facil
itation site is located away from a secretory trigger mediating exocytosis;
otherwise, the facilitation site would be saturated by each action potenti
al. Our simulations account for many characteristics of facilitation and ef
fects of exogenous buffer, and suggest that facilitation is caused by resid
ual calcium gaining access to a site distinct from the secretory trigger th
rough restricted diffusion.