Amyloid Oligomers Alter The Conductance Of The Gramicidin Channel

Abstract

Amyloid oligomers alter the conductance of the gramicidin channel.Our previous data suggest that Aβ does not itself contribute a new intrinsic conductance such as ion channel to the membrane, but it does seem to alter its physical properties, specifically increasing the apparent dielectric constant of hydrocarbon region. This effect could in turn affect the properties of membrane ion channels.In order to test this notion we compared the effects of amyloid oligomers on the single channel conductance of gramicidin in 2 M NaCl and CsCl. Amyloid oligomers increase the single channel conductance in NaCl from 13 to 16 pS, but the situation in CsCl is more complicated. In CsCl, the single channel conductance histogram shows two peaks, one with a conductance essentially the same as control (42 pS) and one with a conductance significantly less than control (28 pS).In terms of a simple three barrier two site model such as that used by Barnett et al., 1986 this suggests that amyloid oligomers lower the energies of both Cs and Na ions in the gramicidin channel, but at different critical locations relative to the barrier profile. For Na+, amyloid oligomers lower the principal central barrier and thus increase the translocation rate of Na+ at a given voltage. For Cs+, amyloid oligomers act as if they lower the energy of the Cs ion in the channel, but in such a way as to increase the depth of one or both of the two wells in the barrier profile.This work was supported by Alzheimer's Association grant IIRG-06-26167 and a grant from the Hillblom Foundation.