Effects of mobile buffers on facilitation: experimental and computational studies.

Facilitation is an important form of short-term plasticity that occurs in most synapses. At crayfish neuromuscular junctions, basal transmission and facilitation were significantly reduced after presynaptic introduction of "fast" high-affinity calcium buffers, and the decay of facilitation was accelerated. The existence of residual calcium during facilitation was also demonstrated. Computational modeling of three-dimensional buffered Ca(2+) diffusion and binding to secretory and facilitation targets suggest that the facilitation site is located away from a secretory trigger mediating exocytosis; otherwise, the facilitation site would be saturated by each action potential. Our simulations account for many characteristics of facilitation and effects of exogenous buffer, and suggest that facilitation is caused by residual calcium gaining access to a site distinct from the secretory trigger through restricted diffusion.