Molecular Pharmacology, Vol 12, 144-155, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

The Influence of Anesthetics and Cholesterol on the Degree of Molecular Organization and Mobility of Ox Brain White Matter

Lipids in Multibilayer Membranes: a Spin Probe Study Using Spectral Simulation by the Stochastic Method

¹ Division of Biological Sciences, National Research Council of Canada, Ottawa, Canada K1A 0R6

The effects of some anesthetics on the molecular arrangement in multibilayer of brain white matter lipids (of low cholesterol content) were studied by observing the ESR spectra of a spin probe derivative of cholestane intercalated in the lipid multilayers. ESR spectra were simulated by a stochastic method, with explicit inclusion of the molecular order parameter and two correlation times. By this method some insight was gained into the arbitrary index or ordering commonly used in these systems. Tetracaine, promazine, chlorpromazine, pentobarbitone, and mepivacaine increased the degree of order in multibilayers containing 5% cholesterol, but did not induce the same high degree of order found at high concentrations of cholesterol. Increasing the concentration of anesthetics eventually produced disorder in the multilayers. The ordering effects of tetracaine and pentobarbitone were reversible. The ordering effect of tetracaine, but not that of pentobarbitone, was potentiated by calcium ions at a concentration (5 mM) which had no intrinisc ordering effect. Multilayers containing up to 5% cholesterol showed a very low degree of order at the molecular level, but above this concentration striking changes in the ESR spectra indicated that the lipid molecules were tending to arrange their long axes close to the normal to the plane of the films. Multilayers of higher cholesterol content showed almost perfect order. The response to cholesterol took place over a very small range of cholesterol concentration, suggestive of a cooperative response. Despite the very large change in order parameter, cholesterol induced no change in the rotational correlation time (mobility).