Abstract

The effect of anesthetics on the rubidium-86 ion efflux from phosphoipid vesicles was studied in the presence of the ionophores gramicidin A and valinomycin and in the absence of ionophores. Anesthetics of known lipid/buffer partition coefficient were used. Pentobarbital, halothane and butanol all increased the three types of ion efflux. The effects were linearly dependent on each anesthetics’ membrane concentration over a range of anesthetic mole fractions in lipid from 0.02 to 0.3, and concentrations known to produce anesthesia produced clearly significant increases in each case. The effect of a given membrane concentration of all the anesthetics on each of the three modes of ion efflux was similar, suggesting that a single perturbation of the lipids is involved in every case. The effects of anesthetics on cation permeability correlated better with their perturbation of lipid bilayers (reported by a freely rotating hydrophobic fluorescent probe [1,6-diphenyl 1,3,5-hexatriene]) than with those reported by spin-labebed lipid probes undergoing anisotropic motion. Coupling between the permeability increases and the perturbation of the bilayer structure was strong, the functional changes being about an order of magnitude larger than the structural changes. The lipid perturbation hypothesis of anesthetic action has been criticized because the structural perturbations observed at anesthetic concentrations are small, but such strong coupling between structural and functional changes may resolve this problem.