Molecular details of anesthetic-lipid interaction.

ABSTRACT

By means of isotopic labeling with deuterium (2H) and observation by nuclear magnetic resonance (NMR), it has been possible to measure the conformational ordering and dynamics of lipids and anesthetics in membranes. The local anesthetic tetracaine causes disordering in the acyl chains of the lipids, very little effect near the glyceryl residue, and minor ordering effects in the charged head group. The anesthetic itself is well ordered within the lipid matrix. The magnitudes of these effects depend upon the nature of the lipid, and upon whether or not the anesthetic is charged. A model can be constructed for the location of the anesthetic within the lipid bilayers. Confirmation of the model comes from Fourier transform infrared spectroscopy (FTIR), which also shows directly the pressure-driven exclusion of local anesthetic from lipid, and the augmentation of this effect by the presence of cholesterol. Future studies by solid-state NMR of protein, and neutron diffraction of specifically deuterated components of anesthetic-nerve systems, should reveal even more precise details of the molecular events involved in anesthesia.