| Abstract: | Accumulation of amyloid (Aβ) 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 Aβ peptides alter the properties of K+ currents in mammalian neurons. We set out to determine the effects of Aβ peptides on the neuronal A‐type K+ channels of Drosophila. Treatment of cells for 18 h with 1 μM Aβ1‐42 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 Aβ1‐42 peptide. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 |
