Single-cell screening of cytosolic [Ca2+] reveals cell-selective action by the Alzheimer's Aβ peptide ion channel

Interaction of the Alzheimer's A beta peptides with the plasma membrane of cells in culture results in chronic increases in cytosolic [Ca2+]. Such increases can cause a variety of secondary effects leading to impaired cell growth or cell degeneration. In this investigation, we made a comprehensive study of the changes in cytosolic [Ca2+] in single PC12 cells and human neurons stressed by continuous exposure to a medium containing A beta 42 for several days. The differential timing and magnitude of the A beta 42-induced increase in [Ca2+] reveal subpopulations of cells with differential sensitivity to A beta 42. These results suggest that the effect produced by A beta on the level of cytosolic [Ca2+] depends on the type of cell being monitored. Moreover, the results obtained of using potent inhibitors of A beta cation channels such as Zn2+ and the small peptide NA7 add further proof to the suggestion that the long-term increases in cytosolic [Ca2+] in cells stressed by continuous exposure to A beta is the result of A beta ion channel activity.