Effects of amyloid peptides on A-type K+ currents of Drosophila larval cholinergic neurons.
Accumulation of amyloid (Abeta) peptides has been suggested to be the primary event in Alzheimer's disease. In neurons, K+ channels regulate a number of processes, including setting the resting potential, keeping action potentials short, timing interspike intervals, synaptic plasticity, and cell death. In particular, A-type K+ channels have been implicated in the onset of LTP in mammalian neurons, which is thought to underlie learning and memory. A number of studies have shown that Abeta peptides alter the properties of K+ currents in mammalian neurons. We set out to determine the effects of Abeta peptides on the neuronal A-type K+ channels of Drosophila. Treatment of cells for 18 h with 1 microM Abeta1-42 altered the kinetics of the A-type K+ current, shifting steady-state inactivation to more depolarized potentials and increasing the rate of recovery from inactivation. It also caused a decrease in neuronal viability. Thus it seems that alteration in the properties of the A-type K+ current is a prelude to the amyloid-induced death of neurons. This alteration in the properties of the A-type K+ current may provide a basis for the early memory impairment that was observed prior to neurodegeneration in a recent study of a transgenic Drosophila melanogaster line over-expressing the human Abeta1-42 peptide.
Department of Human Anatomy and Genetics, MRC Functional Genetics Unit, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom. jackie.kidd@physiol.ox.ac.uk
Jackie F
JF
Kidd
Laurence A
LA
Brown
David B
DB
Sattelle
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D015221:Potassium Channels; C075222:amyloid beta-protein (1-42)