Apoptotic insults impair Na + , K + - ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress Xue

pump) acts as an electrogenic ion transporter in the plasma membrane of all mammalian cells, each cycle of Na + , K +-pump activity extrudes three Na + ions from the cell, moves two K + ions into the cell and uses 1 ATP (Rakowski et al., 1989). The primary role of the Na + , K +-pump is therefore to maintain high intracellular K + and low intracellular Na +. Failure of the Na + , K +-pump results in depletion of intracellular K + , accumulation of intracellular Na + , and, consequently, leads to membrane depolarization and increases in intracellular free Ca 2+ ([Ca 2+ ] i) due to activation of voltage-gated Ca 2+ channels and a reversed operation of the A central role for the Na + , K +-pump in pathogenesis has been widely implicated, particularly in heart ischemia (Ziegelhoffer et al., 2000). Blocking the Na + , K +-pump can induce apoptosis (Olej et al., 1998; Chueh et al., 2001) or a 'hybrid death' containing both apoptotic and necrotic components in individual neurons (Xiao et al., 2002). Conversely, a recent study showed that apoptotic thymocytes had decreased protein levels of the Na + , K +-ATPase (Mann et al., 2001). Whether the apoptotic process may alter the Na + , K +-pump activity, however, is still an open question and has so far not been directly investigated.