Alzheimer's disease amyloid β-protein forms Zn2+-sensitive, cation- selective channels across excised membrane patches from hypothalamic neurons

Abstract

We have previously shown that the 40-residue peptide termed amyloid β- protein (AβP[1-40]) in solution forms cation-selective channels across artificial phospholipid bilayer membranes. To determine whether AβP[1-40] also forms channels across natural membranes, we used electrically silent excised membrane patches from a cell line derived from hypothalamic gonadotrophin-releasing hormone GnRH neurons. We found that exposing either the internal or the external side of excised membrane patches to AβP[1-40] leads to the spontaneous formation of cation-selective channels. With Cs+ as the main cation in both the external as well as the internal saline, the amplitude of the AβP[1-40] channel currents was found to follow the Cs+ gradient and to exhibit spontaneous conductance changes over a wide range (50-500 pS). We also found that free zinc (Zn2+), reported to bind to amyloid β-protein in solution, can block the flow of Cs+ through the AβP[1-40] channel. Because the Zn2+ chelator o-phenanthr