title: Single-cell screening of cytosolic [Ca(2+)] reveals cell-selective action by the Alzheimer's Aβ peptide ion channel.
abstract: Interaction of the Alzheimer's Aβ peptides with the plasma membrane of cells in culture results in chronic increases in cytosolic [Ca(2+)]. 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 [Ca(2+)] in single PC12 cells and human neurons stressed by continuous exposure to a medium containing Aβ42 for several days. The differential timing and magnitude of the Aβ42-induced increase in [Ca(2+)] reveal subpopulations of cells with differential sensitivity to Aβ42. These results suggest that the effect produced by Aβ on the level of cytosolic [Ca(2+)] depends on the type of cell being monitored. Moreover, the results obtained of using potent inhibitors of Aβ cation channels such as Zn(2+) and the small peptide NA7 add further proof to the suggestion that the long-term increases in cytosolic [Ca(2+)] in cells stressed by continuous exposure to Aβ is the result of Aβ ion channel activity.
authors.affiliation: Department of Anatomy, Physiology and Genetics, and Institute for Molecular Medicine, Uniformed Services University School of Medicine, USUHS, Bethesda, MD, 20814, USA.
authors.forename: Hopi
authors.initials: H
authors.lastname: Lin
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Arispe
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D015032:Zinc / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D007473:Ion Channels; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42); D015032:Zinc; D002118:Calcium