Figure 7. Volatile anesthetics reduced presynaptic transmitter release, possibly via a depression of calcium influx into nerve terminals, observed as an increase in excitatory postsynaptic potential facilitation. Facilitation occurs after calcium entry into a nerve terminal, secondary to action potential-induced opening of voltage-operated calcium channels (VOCC; A). Calcium influx causes vesicle release and promotes vesicle docking. The calcium-induced docking after the first of a pair of action potentials (B) promotes increased transmitter release, because more vesicles dock and may be released after the second action potential. Facilitation increases with each stimulus evoked action potential until all docking/release sites become occupied, or until action potentials are separated by enough time to allow undocking (500–1,000 ms). Vesicle docking and release could be differentially controlled by calcium (C); with low calcium concentrations promoting vesicle docking whereas higher concentrations cause release. Facilitation increases, but release decreases when calcium influx is reduced (e.g. in low extracellular calcium). Anesthetics could act at any of a number of sites to depress transmitter release and increase facilitation, because the process of release is known to involve several proteins associated with vesicle and nerve terminal membranes (D). A simple explanation would be that anesthetics depress calcium channels in presynaptic terminals, [19]but this could come about via actions on synaptotagamin, or syntaxin, which are known to bind to voltage operated calcium channels and form a vesicle docking complex (together with SNAP, VAMP, synaptophysin, TAP, actin, and other proteins). [52].