Soluble beta-amyloid induction of Alzheimer's phenotype for human fibroblast K+ channels.
Although beta-amyloid is the main constituent of neurite plaques and may play a role in the pathophysiology of Alzheimer's disease, mechanisms by which soluble beta-amyloid might produce early symptoms such as memory loss before diffuse plaque deposition have not been implicated. Treatment of fibroblasts with beta-amyloid (10 nM) induced the same potassium channel dysfunction previously shown to occur specifically in fibroblasts from patients with Alzheimer's disease--namely, the absence of a 113-picosiemen potassium channel. A tetraethylammonium-induced increase of intracellular concentrations of calcium, [Ca2+]i, a response that depends on functional 113-picosiemen potassium channels, was also eliminated or markedly reduced by 10 nM beta-amyloid. Increased [Ca2+]i induced by high concentrations of extracellular potassium and 166-picosiemen potassium channels were unaffected by 10 nM beta-amyloid. In Alzheimer's disease, then, beta-amyloid might alter potassium channels and thus impair neuronal function to produce symptoms such as memory loss by a means other than plaque formation.
Etcheberrigaray
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Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Ito
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Kim
C S
CS
Alkon
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DL
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D010641:Phenotype; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D012995:Solubility; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011189:Potassium Chloride; D001839:Bombesin; D002118:Calcium; D004121:Dimethyl Sulfoxide