Suppression of an amyloid beta peptide-mediated calcium channel response by a secreted beta-amyloid precursor protein

Secreted isoforms of the beta-amyloid precursor protein potently enhance ne uronal survival in cell cultures exposed to toxic amyloid beta peptide. Low ering of intracellular calcium levels to offset the increases in intraneuro nal calcium caused by amyloid beta peptide is thought to underly this neuro protection, Because we have shown previously that an amyloid beta peptide-m ediated potentiation of calcium channel currents may contribute to this cyt osolic calcium overload, the present study examined the effects of a secret ed beta-amyloid precursor protein on the calcium channel response to amyloi d beta peptide. When compared with untreated cultured rat hippocampal neuro ns, cells that underwent a 24 h preincubation with beta-amyloid precursor p rotein 751 displayed decreases in the relative size of the calcium channel response to amyloid P peptide. A membrane-permeable analog of cyclic GMP, a second messenger believed to be involved in the calcium regulation process mediated by beta-amyloid precursor proteins, also attenuated the modulator y calcium channel response. Coapplication of beta-amyloid precursor protein 751 with amyloid beta peptide did not alter calcium channel response to am yloid beta peptide. Taken together, these findings suggest that secreted be ta-amyloid precursor proteins can suppress a calcium channel response to am yloid beta peptide that is potentially injurious to the cell, and as such, may define a neuroprotective mechanism that is specific for amyloid beta to xicity. (C) 1999 IBRO, Published by Elsevier Science Ltd.