AIM: To study the effects of presenilin-1 (PS-1), presenilin-2 (PS-2), and amyloid beta-protein precursor (APP695) on delayed rectifier potassium channels (IK) in the cultured rat hippocampal neurons. METHODS: PS-1, PS-2, and APP695 were transfected into the cultured rat hippocampal neurons by transient transfection techniques. The IK current was observed by the whole cell patch-clamp techniques. RESULTS: IK was increased in cultured rat hippocampal neurons, after transient transfection of PS-1, PS-2, and APP695. IK amplitudes and densities were significantly increased from (1689±412) pA, (48±18) pA/pF (mock cells, GFP alone, n=17) to (5565±1403) pA, (252±107) pA/pF (PS-1/GFP, n=22, P<0.01), (3804±1651) pA , (120±58) pA/pF( PS-2/GFP, n=16, P<0.01), and (4978±904) pA, (218±70) pA/pF (APP695, n=22, P<0.01). But PS-1, PS-2, and APP695 did not alter the activa- tion curve of IK (P>0.05). CONCLUSION: Overexpression of PS-1, PS-2, and APP695 increased IK in the cultured rat hippocampal neurons. The upregulation of IK may be related to neuronal apoptosis after PS-1, PS-2, and APP695 were transfected.