  A large and diverse array of small hydrophobic molecules induce general
anesthesia. Their efficacy as anesthetics has been shown to correlate both with
their affinity for a hydrophobic environment and with their potency in
inhibiting certain ligand gated ion channels. Here we explore the effects that
n-alcohols and other liquid anesthetics have on the two-dimensional miscibility
critical point observed in cell derived giant plasma membrane vesicles (GPMVs).
We show that anesthetics depress the critical temperature (Tc) of these GPMVs
without strongly altering the ratio of the two liquid phases found below Tc.
The magnitude of this affect is consistent across n-alcohols when their
concentration is rescaled by the median anesthetic concentration (AC50) for
tadpole anesthesia, but not when plotted against the overall concentration in
solution. At AC50 we see a 4{\deg}C downward shift in Tc, much larger than is
typically seen in the main chain transition at these anesthetic concentrations.
GPMV miscibility critical temperatures are also lowered to a similar extent by
propofol, phenylethanol, and isopropanol when added at anesthetic
concentrations, but not by tetradecanol or 2,6 diterbutylphenol, two structural
analogs of general anesthetics that are hydrophobic but have no anesthetic
potency. We propose that liquid general anesthetics provide an experimental
tool for lowering critical temperatures in plasma membranes of intact cells,
which we predict will reduce lipid-mediated heterogeneity in a way that is
complimentary to increasing or decreasing cholesterol. Also, several possible
implications of our results are discussed in the context of current models of
anesthetic action on ligand gated ion channels.
