Amyloid Ion Channels: A Porous Argument or a Thin Excuse?

Over the past decade, a number of groups have reported that oligomeric intermediates populated during the conversion of proteins from a monomeric disaggregated state into amyloid fibrils can permeabilize lipid bilayers and cell membranes. Some of these studies have presented electrical current traces that suggest the formation of discrete oligomeric membrane ion channels, which exhibit selectivity toward cations that can be blocked by a variety of reagents. In this issue, Sokolov et al. (p. 637) use carefully prepared oligomers of the amyloid-β peptide (Aβ), combined with sensitive current measurements capable of detecting the properties of single ion channels to examine the effects of the oligomers on membrane conductance. They conclude that Aβ oligomers clearly cause an increase in membrane permeability, but convincingly rule out any significant formation of discrete ion channels in their samples. Instead, it appears that the oligomers may interfere with the...