UC Irvine

The impact of synthetic amyloid β (1–42) (Aβ_1–42) oligomers on biophysical properties of voltage-gated potassium channels Kv 1.3 and lipid bilayer membranes (BLMs) was quantified for protocols using hexafluoroisopropanol (HFIP) or sodium hydroxide (NaOH) as solvents prior to initiating the oligomer formation. Regardless of the solvent used Aβ_1–42 samples contained oligomers that reacted with the conformation-specific antibodies A11 and OC and had similar size distributions as determined by dynamic light scattering. Patch-clamp recordings of the potassium currents showed that synthetic Aβ_1–42 oligomers accelerate the activation and inactivation kinetics of Kv 1.3 current with no significant effect on current amplitude. In contrast to oligomeric samples, freshly prepared, presumably monomeric, Aβ_1–42 solutions had no effect on Kv 1.3 channel properties. Aβ_1–42 oligomers had no effect on the steady-state current (at −80 mV) recorded from Kv 1.3-expressing cells but increased the conductance of artificial BLMs in a dose-dependent fashion. Formation of amyloid channels, however, was not observed due to conditions of the experiments. To exclude the effects of HFIP (used to dissolve lyophilized Aβ_1–42 peptide), and trifluoroacetic acid (TFA) (used during Aβ_1–42 synthesis), we determined concentrations of these fluorinated compounds in the stock Aβ_1–42 solutions by ¹⁹F NMR. After extensive evaporation, the concentration of HFIP in the 100× stock Aβ_1–42 solutions was ∼1.7 μM. The concentration of residual TFA in the 70× stock Aβ_1–42 solutions was ∼20 μM. Even at the stock concentrations neither HFIP nor TFA alone had any effect on potassium currents or BLMs. The Aβ_1–42 oligomers prepared with HFIP as solvent, however, were more potent in the electrophysiological tests, suggesting that fluorinated compounds, such as HFIP or structurally-related inhalational anesthetics, may affect Aβ_1–42 aggregation and potentially enhance ability of oligomers to modulate voltage-gated ion channels and biological membrane properties.