Potassium channel openers prevent beta-amyloid toxicity in bovine vascular endothelial cells.
There is increasing evidence that the cerebrovasculture may be involved in the pathology of Alzheimer's disease. Here, we report that potassium channel openers (KCOs) inhibit dose and time dependent necrosis induced by beta-amyloid (Abeta) in cultured vascular endothelial cells. Cell proliferation rate was assayed by a colorimetric method. Abeta cytotoxicity and inhibition by the K(ATP) channel opener diazoxide and the K(Ca) channel opener NS1619 was correlated with changes in nitric oxide (NO) production. The protective effects were partly blocked by potassium channel blockers. Toxicity of Abeta and KCO protection was verified by histological examination of endothelial cells with scanning electron microscopy. eNOS levels in endothelial cells were not changed by any of the treatments. The results suggest that disruption of K(+) channels function may be a critical step in Abeta-induced cytotoxicity in endothelial cells by alteration of NO release.
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Department of Physiology, College of Medicine, MDC 8, 12901 Bruce B Downs Boulevard, University of South Florida, Tampa, FL 33612-4799, USA.
Sutton
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ET
Hellermann
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Price
J M
JM
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001921:Brain / Q000098:blood supply; D002417:Cattle; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D005905:Glyburide / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D001562:Benzimidazoles; D015221:Potassium Channels; C086491:NS 1619; D019789:Tetraethylammonium; D003981:Diazoxide; D005905:Glyburide