Aim: 

Amyloid b peptide 1–40 (AbP1-40) and amyloid b1-42 (AbP1-42) are the major components of senile plaques, which are one of the pathological features of Alzheimer's disease (AD). We analyze the capacity of AbP1-42 to incorporate and form ion channels in planar lipid membranes (PLMs). Further, we investigate the role of calcium ions on AbP1-42 incorporation, channel formation and activity.

Methods: 

Channel activity was monitored by means of the voltage-clamp technique. AbP1-42 peptide( (5*10^-8M) was incorporated into a PLM made up of phosphatidylcholine (POPC): cholesterol (Ch) (70:30,w:w) in 1% of n-decane, in absence and in presence of CaCl₂ (2.50*10^-4M). In all experiments, the salt solution used was KCl 0.1M, pH = 7.

Results: 

The incorporation of AbP1-42 into PLMs causes discrete current jumps that fluctuate between conductive and nonconductive states, compatible with channel-type opening and closure with different conductance levels, lifetimes and occurrence frequencies. The addition of Ca⁺⁺ to the cis side of the medium containing AbP1-42 leads to a gradual decrease in channel activity as compared to control conditions (AbP1-42 alone). Preincubating AbP1-42 with Ca⁺⁺, for as long as 24 h, leads to a drastic block of channel activity.

Conclusions: 

The data show that AbP1-42 incorporates into PLMs made up of POPC: Ch and forms voltage-dependent ion channels. Upon Ca⁺⁺ addition, channel activity gradually decreases until coming to a standstill. This suggests that Ca⁺⁺ might induce a change of peptide, incompatible with its incorporation into the membrane. This is consistent with preliminary results obtained with circular dichroism. Owing to the complexity of the interplay between peptide and Ca⁺⁺, further studies are necessary to clarify this aspect.