The Effects of Propofol, Sevoflurane and Isoflurane on Lipid Membrane Fluidity at Clinic Concentrations

In this study, we compare the effects of three clinically significant anesthetic drugs: propofol, sevoflurane and isoflurane, on lipid membrane fluidity. To get complete picture, two representative model lipid membrane systems (pure DPPC and a 5-lipids mixture that mimics brain endothelial cell membrane) and red blood cells were chosen. Lipid membrane systems were labeled with Dipyrene-PC fluorescent probe, whose excimer/monomer (E/M) fluorescence peak ratio showed an immediate increase after adding the drugs, indicating a sharp increase of membrane fluidity. We studied clinical concentrations of 10µM propofol, 0.5mM sevoflurane and 1mM isoflurane. The fluidity increase at these concentrations on DPPC lipid bilayer are similar, and all three drugs are quite effective to loosen up the highly ordered lipid domains of saturated lipids. The supra-clinical concentrations of these drugs, 100µM propofol, 2mM sevoflurane and 5mM isoflurane, have also been examined. The magnitude of increases of E/M ratio in the 5-lipids system were smaller than that in DPPC bilayer. Furthermore, washed human red blood cells (RBC) were labeled with TMA-DPH fluorescent probe and fluorescence anisotropy measurements were carried out. At clinical concentrations, the decreases of TMA-DPH anisotropy were comparable for isoflurane and sevoflurane, and the effects are more than that of 174mM ethanol, which is ten times the legal alcohol limit level in human blood. However, the anisotropy increased after adding propofol, likely due the binding of propofol to certain proteins in RBC. All these findings depict that these anesthetic drugs at clinical concentrations have similar effects on a wide range of lipid membrane systems, and they significantly and rapidly increase lipid membrane fluidity.