Effects of lidocaine on the expansion of lipid monolayer at air/water interface in relation to the local anesthesia

Lidocaine compounds have widely been used as local anesthetics. Regarding the molecular mechanism for anesthesia by local anesthetics, two hypotheses have been proposed. The first one is that molecules of local anesthetics penetrate into the hydrophobic region of cell membrane and expand the membrane volume, resulting in a change of protein conformation that blocks sodium permeability. The second hypothesis is that molecules of local anesthetics are directly adsorbed into the receptors of anesthetics in the protein channel without expanding the cell membrane. However, these proposals have never been examined systematically. In this study, the expansion of cell membrane by lidocaine compounds was investigated by employing lipid monolayer at the air/water interface as the mimetic system for cell membrane. It was found that oil-soluble lidocaine contracted the area/molecule of lipids in the monolayer of phosphatidyl choline, sphingomyelin, DS-PL95E and lipoid, but expand the monolayer of phosphatidyl ethanolamine only in a certain range of mixing ratios. Thus, this study can provide an evidence that lidocaine yields anesthesia effect by adsorbing into receptors in the protein channel rather than expanding the cell membrane.