Abeta(25-35) and Abeta(1-40) act on different calcium channels in CA1 hippocampal neurons.
The acute effects of beta-amyloid (25-35) and (1-40) on high voltage activated calcium channels were compared in CA1 pyramidal cells of adult mouse hippocampal slices using the whole-cell patch-clamp recording. Bath application of oligomeric beta-amyloid (25-35) reversibly increased the barium current (I(Ba)) to 1.61 (normalized amplitude), while oligomeric beta-amyloid (1-40) reversibly enhanced the I(Ba) to 1.74. Reverse-sequence beta-amyloid [(35-25) and (40-1)] had no effect. The effect of beta-amyloid (25-35) was blocked by nifedipine, a selective antagonist of L-type calcium channels. In contrast, the effect of beta-amyloid (1-40) was not blocked by nifedipine and I(Ba) was enhanced to 4.96. It is concluded that these oligomeric peptides may act through different types of calcium channels and/or receptors. The toxicity of Abeta(25-35) implicates a potentiation of L-type calcium channels while the one of Abeta(1-40) is related to an increase of non-L-type calcium channels, which may involve an increase in transmitter release.
Rovira
Catherine
C
Neurobiologie des Processus Adaptatifs, UMR 7102, CNRS et Université Pierre et Marie Curie, Lab. Développement et Vieillissement du Système Nerveux, 9 quai Saint Bernard, 75005, Paris, France. catherine.rovira@snv.jussieu.fr
Arbez
Nicolas
N
Mariani
Jean
J
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D002478:Cells, Cultured; D004553:Electric Conductivity; D006624:Hippocampus / Q000166:cytology*; D007700:Kinetics; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D001464:Barium; D009543:Nifedipine