A universal mechanism for the action of general anesthetics (GA) is not yet available. In this study, we investigated the interaction between halothane and 1,2-dipalmitoyl-sn-3-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-3-glycero-3-phosphocholine (DOPC) bilayers labeled with Laurdan, Prodan, and NBD-C6-PC as the reporter probes using steady-state fluorescence spectroscopy. We have evidence that halothane is located on the acyl chain side, near the headgroup region of the bilayer. Additionally, we find that halothane may be inhomogeneously distributed within DOPC and DPPC bilayers. We also show data that indicate halothane increases the free volume available to fluorescent probes. Differential scanning calorimetry and UV scanning calorimetry experiments were implemented to further observe the effects of halothane addition to the DPPC lipid bilayer. A significant shift of the phase-transition temperature of the DPPC system was observed. Our findings suggest that general anesthetic – lipid bilayer interactions may play a significant role in the overall mechanism of anesthetic action, and these effects should not be ignored when interactions between membrane proteins and anesthetics are considered.Key words: liposomes, anesthesia, fluorescence, phase transition, phospholipid bilayers.

Atomic force microscopy (AFM) was used to study the effect of the general anesthetic halothane on a supported DOPC phospholipid bilayer, under conditions of high anaesthetic loading. The presence of the anaesthetic in the lipid-induced restructuring of the supported bilayer, erosion of the bilayer from the mica surface, and the formation of lipid aggregates. Addition of halothane to lipid vesicles prior to adsorption on the mica surface inhibited the lysis of adsorbed vesicles and thus no planar bilayer formation was observed.Key words: lipid bilayer restructuring, atomic force microscopy, halothane, anesthesis.

In this study atomic force microscopy (AFM) was used to study the effect of halothane on a supported dioleoylphosphatidylcholine (DOPC) bilayer under conditions of high anaesthetic loading. In a previous study we demonstrated that bilayer restructuring occurs as a result of halothane incorporation. Force measurements using AFM indicate an initial decrease in adhesive forces and compressibility between the bilayer and AFM tip, followed by an increase in adhesion properties as a function of incubation time. This effect is attributed to the location and dynamic redistribution of halothane within the bilayer.