|
|
|
|
|
|
|
Free Newsletters
Archive
My Subscriptions
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE
Job Seeker Login
Most Recent Jobs
Browse Biotech Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers
Regional News
US & Canada
Biotech Bay
Biotech Beach
Genetown
Pharm Country
BioCapital
BioMidwest
Bio NC
BioForest
Southern Pharm
BioCanada East
US Device
Europe
Asia
Market Summary
News
IPOs
Company Profiles
Companies
Events
Research Store
Biotech Events
Post an Event
Real Estate
Business Opportunities
|
|
|
|
PLoS By Category | Recent
PLoS Articles
|
|
Anesthesiology and Pain Management - Biophysics
|
Effect of Synthetic Aß Peptide Oligomers and Fluorinated Solvents on Kv1.3 Channel Properties and Membrane Conductance
Published:
Thursday, April 26, 2012
Author:
Maria I. Lioudyno et al.
by Maria I. Lioudyno, Matteo Broccio, Yuri Sokolov, Suhail Rasool, Jessica Wu, Michael T. Alkire, Virginia Liu, J. Ashot Kozak, Philip R. Dennison, Charles G. Glabe, Mathias Lösche, James E. Hall
The impact of synthetic amyloid ß (1–42) (Aß1–42) 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 Aß1–42 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 Aß1–42 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, Aß1–42 solutions had no effect on Kv 1.3 channel properties. Aß1–42 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 Aß1–42 peptide), and trifluoroacetic acid (TFA) (used during Aß1–42 synthesis), we determined concentrations of these fluorinated compounds in the stock Aß1–42 solutions by 19F NMR. After extensive evaporation, the concentration of HFIP in the 100× stock Aß1–42 solutions was ~1.7 µM. The concentration of residual TFA in the 70× stock Aß1–42 solutions was ~20 µM. Even at the stock concentrations neither HFIP nor TFA alone had any effect on potassium currents or BLMs. The Aß1–42 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 Aß1–42 aggregation and potentially enhance ability of oligomers to modulate voltage-gated ion channels and biological membrane properties.
More...
|
|
|
 |
|
|
|
|
|
|
|
|