Figure 1.

Schematic diagram of the tight coupling between neuronal activity and energy metabolism. Depolarizing neuronal activity requires the action of Na⁺K⁺ATPase and other ATPases to repolarize the membrane for reactivation. This is the single most energy-consuming function of neurons. Such energy demand is met under normal conditions by increased blood flow and glucose utilization and increased cellular respiration in the mitochondria, where electron transport is coupled to oxidative phosphorylation, resulting in the synthesis of ATP. Cytochrome c oxidase (COX) is the terminal enzyme of the electron transport chain and reflects the oxidative capacity of neurons. The hydrolysis of ATP by the ATPases yields ADP, which is used to resynthesize ATP and is itself a controlling factor for cellular respiration.