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The lateral pressure profile in membranes: a physical mechanism of general anesthesia.

1. A lipid-mediated mechanism of general anesthesia is suggested and investigated using lattice statistical thermodynamics. 2. Anesthetics are predicted to shift the distribution of lateral pressure within a lipid bilayer, and thus alter the mechanical work required to open ion channel proteins, if channel opening is accompanied by a non-uniform change in cross-sectional area of the protein. 3. Calculations based on this mechanical thermodynamic hypothesis yield qualitative agreement with anesthetic potency at clinical anesthetic membrane concentrations, and predict the alkanol cutoff and anomalously low potencies of strongly hydrophobic molecules with little attraction for the aqueous interface, such as perfluorocarbons.