beta-Amyloid protein amplifies calcium signalling in central neurons from the adult mouse.
The role of beta-amyloid in Alzheimer's disease and its cellular mechanism of action are still unclear. Based on observations that beta-amyloid influences neuronal calcium homeostasis we investigated the effect of the peptide on K(+)-induced enhancement of free intracellular calcium in dissociated neurons from adult mice. Preincubation with beta-amyloid fragment 25-35 at concentrations > or = 0.05 mumol/l resulted in marked amplification of the K(+)-induced Ca2+ response. This effect was also observed with fragment 1-40, whereas fragment 1-28 or 12-28 did not affect the Ca2+ response. This preparation therefore presents a valuable model to investigate the action of beta-amyloid ex vivo in individual animals. Our findings suggest a small but consisting destabilizating effect of beta-amyloid on neuronal Ca2+ homeostasis resulting in chronically increased neuronal vulnerability.
Hartmann
H
H
Dept. Psychopharmacology, Central Institute of Mental Health, Mannheim, FRG.
Eckert
A
A
Müller
W E
WE
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011188:Potassium; D002118:Calcium