Amyloid beta peptides mediate hypoxic augmentation of Ca2+ channels

Clinical studies indicate that neurodegeneration caused by Alzheimer's amyl oid beta peptide (A betaP) formation can be triggered or induced by prolong ed (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 s elective 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 no t by A betaP(40-1). Potentiation of L-type currents was also induced by exp osure to A betaP(25-35). Our results indicate that hypoxia induces enhancem ent of Ca2+ channels, which is mediated by increased APP formation.