Vol. 90, pp. 567–571, January 1993 | NELSON ARISPE, EDUARDO ROJAS, AND HARVEY B. POLLARD
The study investigates the formation of calcium channels by amyloid β protein (AβP) in phospholipid bilayers. AβP, a peptide implicated in Alzheimer's disease, was incorporated into phosphatidylserine liposomes and then fused with a planar bilayer. The AβP peptide formed cation-selective channels, generating linear current-voltage relationships in symmetrical solutions. The permeability ratio for the open AβP channel was estimated to be 11 (P_K/P_Ca). The permeability sequence for different cations was determined to be P_Ca > P_Li > P_Ca ≥ P_K > P_Na. The AβP-channel current was reversibly blocked by tromethamine (millimolar range) and irreversibly by aluminum ions (micromolar range). The blockade by tromethamine and aluminum depends on the transmembrane potential, suggesting direct interaction between these substances and the AβP channel. The findings suggest that the channel activity of AβP may contribute to its neurotoxic effects and that screening compounds for their ability to block or modify AβP channels could be a useful strategy for drug discovery in treating Alzheimer's disease.The study investigates the formation of calcium channels by amyloid β protein (AβP) in phospholipid bilayers. AβP, a peptide implicated in Alzheimer's disease, was incorporated into phosphatidylserine liposomes and then fused with a planar bilayer. The AβP peptide formed cation-selective channels, generating linear current-voltage relationships in symmetrical solutions. The permeability ratio for the open AβP channel was estimated to be 11 (P_K/P_Ca). The permeability sequence for different cations was determined to be P_Ca > P_Li > P_Ca ≥ P_K > P_Na. The AβP-channel current was reversibly blocked by tromethamine (millimolar range) and irreversibly by aluminum ions (micromolar range). The blockade by tromethamine and aluminum depends on the transmembrane potential, suggesting direct interaction between these substances and the AβP channel. The findings suggest that the channel activity of AβP may contribute to its neurotoxic effects and that screening compounds for their ability to block or modify AβP channels could be a useful strategy for drug discovery in treating Alzheimer's disease.