Influence of location of a fluorescent zinc probe in brain slices on its response to synaptic activation

The precise role of the high concentration of ionic zinc found in the synaptic vesicles of certain glutamatergic terminals is unknown. Fluorescent probes with their ability to detect ions at low concentrations provide a powerful approach to monitoring cellular Zn2+ levels. In the last few years, a number of fluorescent probes (indicators) have been synthesized that can be used to visualize Zn2+ in live cells. The interpretation of data gathered using such probes depends crucially on the location of the probe. Using acutely prepared hippocampal slices, we provide evidence that the Zn2+ probes, ZnAF-2 and ZP4, are membrane permeant and are able to pass into synaptic vesicles. In addition, we show that changes in fluorescence of the Zn2+ probes can be used to monitor presynaptic activity; however, these changes are inconsistent with Zn2+ release.