Chronic exposure of NG108-15 cells to amyloid beta peptide (A beta(1-42)) abolishes calcium influx via N-type calcium channels.
We investigated whether amyloid-beta-peptide (A beta(1-42)) has an effect on the elevations of the intracellular concentration of Ca2+ ions ([Ca2+]i) induced by depolarizations of NG108-15 cells and on related Ca2+ channels. A beta(1-42) (10-1000 nM) had no immediate effect on depolarization-induced [Ca2+]i elevations. [Ca2+]i increases were slightly diminished in cells grown in the presence of 100 or 1000 nM A beta(1-42). Nifedipine (1 microM) reduced these elevations equally in cells grown in the absence or presence of A beta(1-42). In contrast, the ability of omega-conotoxin GVIA to diminish the depolarization-induced [Ca2+]i responses became lost in cells grown in the presence of 100 nM A beta(1-42). This indicates that the influx of calcium through the N-type Ca2+ channels was compromised by the chronic exposure of cells to a submicromolar concentration of A beta(1-42), presumably because of impairement of their function or diminished expression. This may be important in the pathogeny of Alzheimer's dementia in view of the pivotal role of N-type Ca2+ channels in neurotransmitter release.
Kasparová
J
J
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
Lisá
V
V
Tucek
S
S
Dolezal
V
V
D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002460:Cell Line; D017136:Ion Transport; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D009543:Nifedipine; D002118:Calcium