Publication Date:
1994-04-08
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Etcheberrigaray, R -- Ito, E -- Kim, C S -- Alkon, D L -- New York, N.Y. -- Science. 1994 Apr 8;264(5156):276-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8146663" target="_blank"〉PubMed〈/a〉
Keywords:
Alzheimer Disease/*metabolism
;
Amyloid beta-Peptides/*pharmacology
;
Bombesin/pharmacology
;
Calcium/metabolism
;
Cell Line
;
Cells, Cultured
;
Dimethyl Sulfoxide/pharmacology
;
Female
;
Fibroblasts/*drug effects/metabolism
;
Humans
;
Male
;
Phenotype
;
Potassium Channel Blockers
;
Potassium Channels/*drug effects/metabolism
;
Potassium Chloride/pharmacology
;
Solubility
;
Tetraethylammonium
;
Tetraethylammonium Compounds/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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