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

The C-terminal 105 amino acid fragment of β-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 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. CT105-induced channels were selective to cations (P(K)/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.