Nature of alcohol and anesthetic action on cooperative membrane equilibria

Abstract

A generalized, colligative thermodynamic framework is used to treat the action of solutes on cooperative membrane equilibria. Configurational entropy, the randomness imparted by solutes through the partitioning or mixing process, is implicated as the energetic driving force for the action of anesthetics on cooperative membrane equilibria. The equilibria predicted to be most sensitive to solute action--in which the dilute solute causes a perturbation equivalent to a large change in temperature--are (1) low-enthalpy processes that coincide with (2) large partitioning differences between states. The model stresses that solutes do not act at a single site, but on both states in an equilibrium, and that the perturbation is determined by the difference in entropy. Evidence for the thermodynamic framework is obtained from the partitioning behavior of the general anesthetic 1-hexanol into a model lecithin (DMPC; 1,2-dimyristoyl-sn-glycero-3-phosphocholine) membrane as a function of temperature and alcohol concentration. The low-enthalpy equilibrium between the gel (L beta') and ripple states (P beta') (pretransition) is more sensitive to 1-hexanol than the high-enthalpy equilibrium between the ripple (P beta') and fluid bilayer states (L alpha) (main transition). The perturbations of both equilibria are accurately described by the colligative thermodynamic framework. The results suggest that alcohols and anesthetics act through entropy to upset the natural thermal balance that maintains native membrane architecture.

A thermochemical analysis of inhalational anesthetics

“…It has been proposed that phase transition of membrane phospholipids is the primary cause of anesthetic action [23,24]. A similar mechanism was later suggested for anesthetic action on membrane proteins [25].…”

Cytotoxicity of millimolar concentrations of ethanol on HepG2 human tumor cell line compared to normal rat hepatocytes in vitro

“…Error bars represent SD concentrations where oxidative stress induced by altered metabolism is supposed to be the major determinant of ethanol toxicity (Kurose et al 1997). At low concentrations the biophysical action of the lipophilic ethanol, such as the interaction with biological membranes and its eect on a variety of membrane-bound proteins, seems to be of major importance (Janes et al 1992).…”

Saturable Ethanol Binding in Rat Liver Microsomes

“…Binding to liposomes was performed as described by Janes et al (14), except that 3 H-labeled sucrose was used as a bulk water marker. The binding is expressed as the molal partition coefficients of the hydrated membrane.…”