beta-Amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus.
The effect of beta-amyloid on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic excitatory postsynaptic currents measured with whole-cell voltage-clamp techniques, was investigated in the rat dentate gyrus in vitro. Application of beta-amyloid (1-40) by extracellular perfusion (200 nM) or intracellularly via the recording pipette (100 nM) resulted in a gradual enhancement of the NMDA receptor-mediated synaptic currents which did not reverse on washout. Basal AMPA receptor-mediated transmission, resting membrane potential or input resistance of the granule cells did not change. These results provide direct evidence that beta-amyloid selectively interacts with the potentially neurotoxic NMDA receptor via a postsynaptic site. It is proposed that this action may help explain the synaptic changes seen in Alzheimer's disease.
Wu
J
J
Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland.
Anwyl
R
R
Rowan
M J
MJ
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate