  Some anesthetics bind and potentiate gamma-aminobutyric-acid-type receptors,
but no universal mechanism for general anesthesia is known. Furthermore, often
encountered complications such as anesthesia induced amnesia are not
understood. General anesthetics are hydrophobic molecules easily dissolving
into lipid bilayers. Recently, it was shown that general anesthetics perturb
phase separation in vesicles extracted from fixed cells. Unclear is whether
under physiological conditions general anesthetics induce perturbation of the
lipid bilayer, and whether this contributes to the transient loss of
consciousness or anesthesia side effects. Here we show that propofol perturbs
lipid nanodomains in the outer and inner leaflet of the plasma membrane in
intact cells, affecting membrane nanodomains in a concentration dependent
manner: 1 {\mu}M to 5 {\mu}M propofol destabilize nanodomains; however,
propofol concentrations higher than 5 {\mu}M stabilize nanodomains with time.
Stabilization occurs only at physiological temperature and in intact cells.
This process requires ARP2/3 mediated actin nucleation and Myosin II activity.
The rate of nanodomain stabilization is potentiated by GABA receptor activity.
Our results show that active nanodomain homeostasis counteracts the initial
disruption causing large changes in cortical actin.
