Synaptic vesicle recruitment for release explored by Monte Carlo simulation at the crayfish neuromuscular junction

Neurotransmission at chemically transmitting synapses requires calcium-medi ated fusion of synaptic vesicles with the presynaptic membrane. Utilizing u ltrastructural information available for the crustacean excitatory neuromus cular junction, we developed a model that employs the Monte Carlo simulatio n technique to follow the entry and movement of Ca2+ ions at a presynaptic active zone, where synaptic vesicles are preferentially docked for release. The model includes interaction of Ca2+ with an intracellular buffer, and v ariable separation between calcium channels and vesicle-associated Ca2+-bin ding targets that react with Ca2+ to trigger vesicle fusion. The end point for vesicle recruitment for release was binding of four Ca2+ ions to the ta rget controlling release. The results of the modeling experiments showed th at intracellular structures that interfere with Ca2+ diffusion (in particul ar synaptic vesicles) influence recruitment or priming of vesicles for rele ase. Vesicular recruitment is strongly influenced by the separation distanc e between an opened calcium channel and the target controlling release, and by the concentration and binding properties of the intracellular buffers, as in previous models. When a single opened calcium channel is very close t o the target, a single synaptic vesicle can be recruited. However, many of the single-channel openings actuated by a nerve impulse are likely to be in effective for release, although they contribute to the buildup of total int racellular Ca2+. Thus, the overall effectiveness of single calcium channels in causing vesicles to undergo exocytosis is likely quite low.