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Role of Potassium Channels in Amyloid‐Induced Cell Death
Author(s) -
Colom Luis V.,
Diaz Maria E.,
Beers David R.,
Neely Alan,
Xie Wenjie,
Appel Stanley H.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70051925.x
Subject(s) - potassium channel , amyloid (mycology) , potassium , programmed cell death , neuroscience , chemistry , microbiology and biotechnology , amyloid β , biophysics , biology , biochemistry , medicine , apoptosis , disease , organic chemistry , inorganic chemistry
Basal forebrain cholinergic neurons are severely depleted early in Alzheimer's disease and appear particularly susceptible to amyloid β‐peptide (Aβ) toxicity in vivo. To model this effect in vitro, a cholinergic septal cell line (SN56) was exposed to Aβ. 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 Aβ 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 Aβ, respectively. Perfusion of SN56 cells with 10–20 m M TEA blocked 71 ± 6 to 92 ± 2% of the outward currents, widened action potentials, elevated [Ca 2+ ] i , and inhibited 89 ± 14 and 68 ± 14% of the Aβ toxicity. High [K + ] o , which depolarizes cell membranes and increases [Ca 2+ ] i , also protected SN56 cells from Aβ 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, Aβ 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 Aβ and MES23.5 cells were not protected by TEA from Aβ toxicity. In contrast, a noncholinergic septal cell line (SN48) that shows minimal outward K + currents was resistant to the toxicity of Aβ. These data suggest that a K + channel with delayed rectifier characteristics may play an important role in Aβ‐mediated toxicity for septal cholinergic cells.