Fig. 6.

NMDA receptor-dependent Ca²⁺ influx is required for mitochondrial depolarization. Ratios of JC-1 aggregate fluorescence over monomer fluorescence were normalized to the value obtained at the second scan; multiple trials were averaged and plotted as a function of time (mean ± SEM). When glutamate (Glu) (100 or 500 μm, data not different and thus combined) was applied in the presence of 5 μmMK801 (at the bar; squares,n = 31), none of the individual neurons met the criteria for depolarization as described in Materials and Methods. Glu (100 or 500 μm; data not different and thus combined) was also applied in the nominal absence of Ca²⁺ (at thebar; triangles,n = 35); none of the individual neurons met the criteria for depolarization, and as reflected in the average increase, 60% of the cells met the criteria for hyperpolarization. CGP-37157 (25 μm, an inhibitor of mitochondrial Na⁺/Ca²⁺ exchange) was applied for 5 min (at the bar) in a set of control experiments and caused a reversible hyperpolarization without exception (diamonds, n = 17).