Effect of anesthetics and pressure on the thermotropic behavior of multilamellar dipalmitoylphosphatidylcholine liposomes.

Abstract

The effects of gaseous anesthetics and pressure on the thermotropic behavior of multilamellar dipalmitoylphosphatidylcholine liposomes were studied by using a highsensitivity differential scanning calorimeter. It was found that halothane and enflurane decreased the transition temperature and increased the width of the transition without affecting the enthalpy change for the main gel-to-liquid crystalline transition. This emonstrated that the anesthetics decreased the degree of cooperative interaction between phospholipid molecules within the bilayer. Increasing the pressure increased the transition temperature but did not affect the transition width or enthalpy change. However, the increase in pressure reversed the effect of anesthetic on both the transition temperature and transition width. It is sugested that an understanding of the effect of anesthetics on the degree of cooperative interaction between phospholipids may be a key to understanding anesthetic action.The physiological effect of inhalation anesthetics is likely a manifestation of the perturbation of membrane functions associated with synaptic transmission of nerve impulses. This conclusion is primarily based on the high degree of correlation between anesthetic potency and lipid solubility (1, 2). Although it is possible that the primary sites of the action of anesthetics are specific membrane proteins, an attractive alternative is that such action is the result of induced changes in the dynamic structure of the lipid matrix.Trudell and coworkers (3) have demonstrated that general anesthetics decrease the gel-to-liquid crystalline phase transition temperature of phospholipid bilayers and that this effect can be reversed by application of moderate pressures [-100 atmospheres (atm) (10 MPa)] to the system. This result is particularly intriguing because the physiological effect can also be reversed by moderate pressures (4). Recently, Trudell (5) developed a phenomenological theory of anesthesia based on the concept of lateral phase separation in the membrane. This theory focuses on the absolute increase in fluidity of the phospholipid matrix caused by anesthetics. It was suggested that, when phase separation no longer exists, membranes are less able to facilitate the protein conformational changes necessary for normal physiological function.In order to assess carefully the effect of the gaseous anesthetics on the thermotropic behavior of lipid bilayers, a detailed study was initiated using a highly sensitive differential scanning calorimeter. In addition, the influence of pressure on this behavior was ascertained by using a pressure cell adapted for this calorimeter. The results of this study show that the general anesthetics halothane (CF3CHBrCl) and enflurane (CHF2OCF2CHFCI) decrease the transition temperature without affecting the enthalpy change for the transition but that the degree of cooperative interaction between phospholipid molecules is decreased. Both these effects can be reversed by the application of moderate pressures. We there...

Miscibility of phosphatidylcholine binary mixtures in unilamellar vesicles: Phase equilibria

“…The effect of acyl chain-length (Shimsbick & McConnell, 1973;Chapman et al, 1974;Lentz et al, 1976;Mabrey & Sturtevant, 1976;Jacobs et al, 1977;Kremer et al, 1977;Lee, 1978;Marcelja & Wolf, 1979;Scott & Cheng, 1979;Freire & Snyder, 1980;Chen & Sturtevant, 1981), polar head group (Blume & Ackerman, 1974;Chapman et al, 1974;Wu & McConnell, 1975;Lentz & Litman, 1978), or perturber molecules such as anesthetics (Jain & Wu, 1977;Mountcastle et al, 1978;Heyn et al, 1981) upon the width of the phase transition, have been reported. The theory on the cooperativity of lipid phase transition in bilayer systems is inconsistent with the idea that the thermotropic phase transition of lipid bilayers follows thermodynamically first-order kinetics.…”

Enthalpy and Volume Changes in Lipid Membranes. I. The Proportionality of Heat and Volume Changes in the Lipid Melting Transition and Its Implication for the Elastic Constants

“…Table 2) is comparable to previous studies for the transition temperature. The value for the proportionality factor, γ, averaged over various literature values yields a mean value γ j ) 7.34‚10 -4 mL/J for DMPC MLV, 12,14,16,20,21 γ j ) 7.07‚10 -4 mL/J for DPPC MLV, 14,16,[19][20][21]39,40 and γ j ) 7.63‚10 -4 mL/J for distearoyl phosphatidylcholine MLV. 13,20 Similar numbers where found for dieladioyl phoshatidylcholine and palmitoyl oleoyl phosphatidylcholine.…”

A scanning calorimetric study of small molecule-lipid bilayer mixtures.

“…The transfer ofsmall molecules from aqueous medium into lipid bilayers is a process that is undoubtedly important in biological membranes and has accordingly received much attention in recent years (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). As discussed by Diamond and Katz (5) and Milgram and Solomon (20), this transfer involves rate processes in addition to the equilibrium distribution of solute between aqueous and lipid phases.…”