Cation selective channels formed by a C-terminal fragment of beta-amyloid precursor protein

The C-terminal 105 amino acid fragment of beta-amyloid precursor protein (CT105) is highly neurotoxic. To obtain insights into its cytotoxic effect, we examined the ionophoric effects of CT105 (10-1000 nM) on artificial lipid membranes. Macroscopic membrane conductance increased with CT105 concentration and its ionophoric effect was comparable to that of amyloid beta protein. The mean unitary conductance of CT105-induced channels was 120 pS and open-state probability was close to 1 at voltages from -80 to +80 mV. CT105induced channels were selective to cations (PK/ P(Cl) = 10.2), being most selective to Ca2+. These findings suggest that CT105 can cause direct neurotoxic effects by forming Ca2+ permeable cation channels on neuronal membranes.