%0 Journal Article
%T Effect of Synthetic A汕 Peptide Oligomers and Fluorinated Solvents on Kv1.3 Channel Properties and Membrane Conductance
%A Maria I. Lioudyno
%A Matteo Broccio
%A Yuri Sokolov
%A Suhail Rasool
%A Jessica Wu
%A Michael T. Alkire
%A Virginia Liu
%A J. Ashot Kozak
%A Philip R. Dennison
%A Charles G. Glabe
%A Mathias Lˋsche
%A James E. Hall
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0035090
%X The impact of synthetic amyloid 汕 (1每42) (A汕1每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 A汕1每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 A汕1每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, A汕1每42 solutions had no effect on Kv 1.3 channel properties. A汕1每42 oligomers had no effect on the steady-state current (at ˋ80 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 A汕1每42 peptide), and trifluoroacetic acid (TFA) (used during A汕1每42 synthesis), we determined concentrations of these fluorinated compounds in the stock A汕1每42 solutions by 19F NMR. After extensive evaporation, the concentration of HFIP in the 100℅ stock A汕1每42 solutions was ~1.7 米M. The concentration of residual TFA in the 70℅ stock A汕1每42 solutions was ~20 米M. Even at the stock concentrations neither HFIP nor TFA alone had any effect on potassium currents or BLMs. The A汕1每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 A汕1每42 aggregation and potentially enhance ability of oligomers to modulate voltage-gated ion channels and biological membrane properties.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035090