Fig. 6.

Schematic representation of potential pathways by which mitochondrial dysfunction could act as an effector of excitotoxic neuronal death. NMDAR overstimulation induces excessive Ca²⁺ influx and abnormal elevations of [Ca²⁺]_i. Mitochondrial Ca²⁺uptake, driven by ΔΨ, attenuates ΔΨ. This, in turn, causes a decrease in ATP synthesis and the opening of the PTP, which collapses ΔΨ. Mitochondrial dysfunction elicits a further reduction in intracellular ATP pools, increases free radical generation, and most likely activates other processes that ultimately contribute to neuronal cell death.