title: Role of potassium channels in amyloid-induced cell death.
abstract: Basal forebrain cholinergic neurons are severely depleted early in Alzheimer's disease and appear particularly susceptible to amyloid beta-peptide (A beta) toxicity in vivo. To model this effect in vitro, a cholinergic septal cell line (SN56) was exposed to A beta. SN56 cells exhibited a tetraethylammonium (TEA)-sensitive outward K+ current with delayed rectifier characteristics. Increases of 64% (+/-19; p < 0.02) and 44% (+/-12; p < 0.02) in K+ current density were noted 6-12 and 12-18 h following the addition of A beta to SN56 cell cultures, respectively. Morphological observation and staining for cell viability showed that 25 +/- 4 and 39 +/- 4% of SN56 cells were dead after 48- and 96-h exposures to A beta, respectively. Perfusion of SN56 cells with 10-20 mM TEA blocked 71 +/- 6 to 92 +/- 2% of the outward currents, widened action potentials, elevated [Ca2+]i, and inhibited 89 +/- 14 and 68 +/- 14% of the A beta toxicity. High [K+]o, which depolarizes cell membranes and increases [Ca2+]i, also protected SN56 cells from A beta toxicity. This effect appeared specific since glucose deprivation of SN56 cells did not alter K+ current density and TEA did not protect these cells from hypoglycemic cell death. Furthermore, A beta was toxic to a dopaminergic cell line (MES23.5) that expressed a K+ current with delayed rectifier characteristics; K+ current density was not altered by A beta and MES23.5 cells were not protected by TEA from A beta toxicity. In contrast, a noncholinergic septal cell line (SN48) that shows minimal outward K+ currents was resistant to the toxicity of A beta. These data suggest that a K+ channel with delayed rectifier characteristics may play an important role in A beta-mediated toxicity for septal cholinergic cells.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Colom
authors.forename: M E
authors.initials: ME
authors.lastname: Diaz
authors.forename: D R
authors.initials: DR
authors.lastname: Beers
authors.forename: A
authors.initials: A
authors.lastname: Neely
authors.forename: W J
authors.initials: WJ
authors.lastname: Xie
authors.forename: S H
authors.initials: SH
authors.lastname: Appel
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016923:Cell Death / Q000502:physiology; D002459:Cell Fusion; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004351:Drug Resistance; D004553:Electric Conductivity; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; D004247:DNA; D011188:Potassium; D002118:Calcium