Amyloid β peptides mediate hypoxic augmentation of Ca2+ channels

Clinical studies indicate that neurodegeneration caused by Alzheimer's amyloid beta peptide (A betaP) formation can be triggered or induced by prolonged (chronic) hypoxia. Here, we demonstrate that 24-h culture of PC12 cells in 10% O-2 leads to induction of a Cd2+-resistant Ca2+ influx pathway and selective potentiation of L-type Ca2+ current. Both effects were suppressed or prevented by a monoclonal antibody raised against the N ' -terminus of A betaP, and were fully mimicked by A betaP(1-4)0 and A alphaP(1-42), but not by A betaP(40-1). Potentiation of L-type currents was also induced by exposure to A betaP(25-35). Our results indicate that hypoxia induces enhancement of Ca2+ channels, which is mediated by increased APP formation.