Zinc-induced aggregation of Aβ (10–21) potentiates its action on voltage-gated potassium channel

Zinc may play an important role in the pathogenesis of Alzheimer’s disease (AD) through influencing the conformation and neurotoxicity of amyloid β-proteins (Aβ). Zn2+ induces rapid aggregation of synthetic or endogenous Aβ in a pH-dependent fashion. Here we show for the first time that Zn2+-induced aggregation of Aβ (10–21) potentiates its action on outward potassium currents in hippocampal CA1 pyramidal neurons. Using the whole-cell voltage-clamp technique, we showed that Aβ (10–21) blocked the fast-inactivating outward potassium current (IA) in a concentration- and aggregation-dependent manner, but with no effect on the delayed rectifier potassium current (IK). Both the unaggregated and aggregated forms of Aβ (10–21) significantly shifted the activation curve and the inactivation curve of IA to more negative potentials. But the aggregated form has more effects than the unaggregated form. These data indicated that aggregation of amyloid fragments by zinc ions is required in order to obtain full modulatory effects on potassium channel currents.