ACTION OF ANAESTHETICS ON PHOSPHOLIPID MEMBRANES

The permeability of 4% phosphatidic acid-96% phosphatidyl choline liposomes to K+ was studied over a temperature range with and without the anaesthetic compounds diethyl ether, chloroform and n-butanol at approximately the concentrations at which they are effective in vivo; the results were compared to the same system when the potassium ionophore, valinomycin, was also present in the liposomes. In all cases the anaesthetic increased the permeability. Arrhenius plots were made to find the enthalpy of activation ΔH* * For reviews of early work see refs. 1 and 2 and differences in the entropy of activation. After correction for anaesthetic partition coefficients at the various temperatures, the enthalpy of activation ΔH* (15.4 ± 1.1 kal · mole-1) was the same whether or not anaesthetics or valinomycin was present. The ΔH* of a system containing valinomycin and anaesthetic was lower, depending on the anaesthetic used. It was deduced that: (1) The cation permeability barrier was located at the aqueous-lipid interface. (2) The anaethetics increased the freedom of movement of groups in the lipid molecule near the interface. (3) The increase in permeability to K+ in the presence of valinomycin was due to an entropy increase in the activated state of approx. 35 cal · mole-1 · degree-1. (4) The increased freedom of movement in the interface when the anaesthetic was present allowed the valinomycin to adopt a more favourable orientation in the interface for the exchange of K+. © 1969.