Chronic exposure of NG108-15 cells to amyloid beta peptide (A beta(1-42)) abolishes calcium influx via N-type calcium channels

We investigated whether amyloid-beta -peptide (A beta (1-42)) has an effect on the elevations of the intracellular concentration of Ca2+ ions ([Ca2+]( i)) induced by depolarizations of NG108-15 cells and on related Ca2+ channe ls. A beta (1-42) (10-1000 nM) had no immediate effect on depolarization-in duced [Ca2+](i) elevations. [Ca2+](i) increases were slightly diminished in cells grown in the presence of 100 or 1000 nM A beta (1-42). Nifedipine (1 muM) reduced these elevations equally in cells grown in the absence or pre sence of A beta (1-42). In contrast, the ability of omega -conotoxin GVIA t o diminish the depolarization-induced [Ca2+](i) responses became lost in ce lls grown in the presence of 100 nM A beta (1-42). This indicates that the influx of calcium through the N-type Ca2+ channels was compromised by the c hronic exposure of cells to a submicromolar concentration of A beta (1-42), presumably because of impairement of their function or diminished expressi on. This may be important in the pathogeny of Alzheimer's dementia in view of the pivotal role of N-type Ca2+ channels in neurotransmitter release.