Abstract
The volatile anesthetic isoflurane (ISO) has previously been shown to increase the fluidity of artificial lipid membranes, but very few studies have used biological cell membranes. Therefore, to investigate whether ISO affects the mobility of membrane proteins, fluorescence‐labeled transferrin receptor (TfR) and glycosylphosphatidylinositol (GPI)‐anchored protein were expressed in human embryonic kidney 293T cells and neural cells and lateral diffusion was examined using fluorescence recovery after photobleaching. Lateral diffusion of the TfR increased with ISO treatment. On the other hand, there was no effect on GPI‐anchored protein. We also used GC/MS to confirm that there was no change in the concentration of ISO due to vaporization during measurement. These results suggest that ISO affects the mobility of transmembrane protein molecules in living cells.
Highlights
The full mechanism of action of volatile anesthetics is not yet known
To investigate the effect of anesthetic drugs on cell membrane fluidity, we analyzed the lateral diffusion of fluorescence-labeled membrane molecules in the presence of anesthetic drugs using fluorescence recovery after photobleaching (FRAP)
We studied the frequently used anesthetic drugs ISO, a volatile anesthetic drug generally used in clinical medicine with an unknown detailed mechanism of action, and MDZ, a benzodiazepine agonist (Fig. 1A)
Summary
The full mechanism of action of volatile anesthetics is not yet known. The complete mechanism underlying the action of volatile anesthetics remains unknown. Tang et al [4] proposed that volatile anesthetics preferentially target the lipid–protein–water interface and not a specific channel protein They simulated the interaction between halothane molecules and the gramicidin A channel using large-scale 2.2-ns all-atom molecular dynamic simulation. Halothane decreased the viscosity (increased fluidity) of the DPPC membrane in a dose-dependent manner They concluded that the presence of volatile anesthetics at the membrane–water interface dampened lipid–water interaction forces and increased membrane fluidity. These findings help our understanding of the distribution and effects of anesthetics within the membranes; the mechanisms in live cell membranes remain elusive. We hypothesized that the heterogeneous distribution of anesthetic molecules in living membranes would result in heterogeneous changes in membrane fluidity
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