Zinc is externalized rather than released during synaptic transmission.

The synaptic vesicles of some glutamatergic terminals contain a high concentration of zinc that serves functions that remain obscure. In this publication we have used the membrane permeant zinc fluophore, ZnAF-2 to determine if zinc is released during the course of synaptic transmission. Stimulation of the slices with either high potassium or electrically, leads to an increase in fluorescence that long outlasts the stimulus and remains elevated for many minutes. We demonstrate that this response is inconsistent with the free release of zinc but is with the presentation of zinc coordinated to macromolecules within the exocytosed vesicles to the extracellular space; a process we term 'externalization'. Our data suggests a novel mechanism of synaptic transmission at zinc-rich glutamatergic terminals that distinguishes them from their metal free counterparts.