Lipid-Dependent Effects of Halothane on Gramicidin Channel Kinetics: A New Role for Lipid Packing Stress

We find that the sensitivity of gramicidin A channels to the anesthetic halothane is highly lipid dependent. Specifically, exposure of membranes made of lamellar DOPC to halothane in concentrations close to clinically relevant reduces channel lifetimes by 1 order of magnitude. At the same time, gramicidin channels in membranes of nonlamellar DOPE are affected little, if at all, by halothane. We attribute this difference in channel behavior to a difference in the stress of lipid packing into a planar lipid bilayer, wherein the higher stress of DOPE packing reduces the degree of halothane partitioning into the hydrophobic interior.