AMPAR-mediated (Zn2+)i rises are mainly dependent on intracellular Zn2+ mobilization. A. AMPAR-mediated (Zn2+)i rises are not modulated by extracellular Zn2+ chelation. FluoZin-3 loaded neurons were exposed, as in Figure 1, to kainate in the presence of the extracellular Zn2+ chelator Ca2+ EDTA (20 liM). Note that the (Zn2+)i rises occurring both during and after kainate exposure are not affected by extracellular chelation of contaminant Zn2+, indicating that the source of these rises is intracellular. B. AMPAR-mediated release of intra-mitochondrial Zn2+. FluoZin-3 loaded cultures were exposed for 5 min to the mitochondrial protonophore, CCCP (1 µM), challenged with 300 µM kainate for 5 min and washed at pH 7.4, in the presence of CCCP. Note that prior exposure to CCCP greatly inhibits subsequent kainate-triggered (Zn2+)i rises, indicating that these two manipulations target a common intracellular Zn2+ pool. Traces show time course of FluoZin-3 ΔF (±SEM), and are derived from > 15 neurons from 3–5 experiments.