TY - JOUR
T1 - Role of potassium channels in amyloid-induced cell death
AU - Colom, Luis V.
AU - Diaz, Maria E.
AU - Beers, David
AU - Neely, Alan
AU - Xie, Wen Jie
AU - Appel, Stanley H.
PY - 1998/5
Y1 - 1998/5
N2 - 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. Morphologica observation and staining for cell viability showed that 25 ± 4 and 39 ± 4% of SN56 cells were dead after 48- add 96-h exposures to Aβ, 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+]1, and inhibited 89 ± 14 and 68 ± 14% of the Aβ toxicity. High [K+](o), which depolarizes cell membranes and increases [Ca2+](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.
AB - 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. Morphologica observation and staining for cell viability showed that 25 ± 4 and 39 ± 4% of SN56 cells were dead after 48- add 96-h exposures to Aβ, 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+]1, and inhibited 89 ± 14 and 68 ± 14% of the Aβ toxicity. High [K+](o), which depolarizes cell membranes and increases [Ca2+](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.
KW - Alzheimer's disease
KW - Amyloid
KW - Cell death
KW - Cholinergic innervation
KW - Potassium channels
UR - http://www.scopus.com/inward/record.url?scp=0031978287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031978287&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1998.70051925.x
DO - 10.1046/j.1471-4159.1998.70051925.x
M3 - Article
C2 - 9572276
AN - SCOPUS:0031978287
VL - 70
SP - 1925
EP - 1934
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -