Effects of anesthetics on divalent cation binding and fluidity of phosphatidylserine vesicles.

Divalent cation binding to sonicated phosphatidylserine (PS), as affected by added anesthetics, was examined by electron paramagnetic resonance, used in conjunction with the paramagnetic Ca2+ analogue Mn2+. Long- and short-chain normal alkanols (up through pentadecanol), benzyl alcohol, chloroform, procaine, and tetracaine all inhibited Mn2+ binding to PS. With increasing chain length, the normal alcohols became more effective in displacing the divalent cation from the vesicles. This appeared to be related to the dependence of alcohol lipid/water partition coefficients on the number of carbons in the methylene chain. Chloroform, on the other hand, although reported to be comparable to hexanol in its partitioning characteristics and anesthetic potency, was a much weaker inhibitor of manganese binding than the latter. The perturbation of PS fluidity by the anesthetics was monitored through EPR spectral observations on a cholestane spin probe. When anesthetic concentrations were adjusted approximately to equalize effects on manganese binding, the lower normal alkanols, benzyl alcohol, and chloroform all fluidized the vesicles substantially, as evidenced by enhanced mobility of the probe. The higher alcohols and the amine anesthetics, in contrast, produced little or no fluidization of the vesicles. The results are discussed in terms of possible molecular explanations for the phenomena and suggested mechanisms for anesthesia.