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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. CT105-induced channels were selective to cations (PK PCl = 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.

(C) 1999 Lippincott Williams & Wilkins, Inc.