Establishment of the Meyer-Overton correlation in an artificial membrane without protein

Abstract

BackgroundThe potency of anesthetics with various structures increases exponentially with lipophilicity, which is the Meyer-Overton (MO) correlation discovered over 120 years ago. The MO correlation was also observed with various biological effects and various chemicals, including alcohols; thus, the correlation represents a fundamental relationship between chemicals and organisms. The MO correlation was explained by the lipid and protein theories, although the debate has not been resolved and the principle remains unknown. MethodsThe gentle hydration method was used to form giant unilamellar vesicles (GUVs) consisting of high- and low-melting phospholipids and cholesterol in the presence of n-alcohols (C2-C12). Confocal fluorescence microscopy was used to determine the percentage of GUVs with domains in relation to the concentrations of n-alcohols. Resultsn-Alcohols inhibited the domain formation of GUVs, and the half inhibitory concentration (IC50) in the aqueous phase decreased exponentially with increasing chain length (lipophilicity). In contrast, the membrane concentrations of alcohols for the inhibition, which is a product of the membrane-water partition coefficient and the IC50 values, remained constant irrespective of the chain length. ConclusionsThe MO correlation is established in artificial lipid membrane, which supports the lipid theory. When alcohols reach the same critical concentration in the membrane, similar biological effects appear irrespective of the chain length, which is the principle underlying the MO correlation. Summary Statementn-Alcohols inhibit the domain formation of giant unilamellar vesicles according to the Meyer-Overton correlation.