Key contributions of the Na~+/H~+ exchanger subunit 1 and HCO_3 transporters in regulating neuronal cell fate in prolonged hypoxia

摘要

While the mammalian brain does have some capability for depressing its metabolism upon oxygen deprivation, such protective mechanisms are known to fail readily in brain ischemia, leading to a series of events that are catastrophic for neurons, including ATP loss, membrane depolarization, and an uncontrolled release of excitatory neurotransmitters (12). Hypoxic injury in neurons is closely linked to a substantial Ca~(2+) overload that plays a central role in excitotoxic cell death (18). In brain tissue, hypoxia induces complex changes in extracellular and intracellular pH, and, under ischemic conditions, numerous studies report a decrease in intracellular pH.