Nuclear Magnetic Resonance Partitioning Studies of Solute Action in Lipid Membranes

INTRODUCTION: Lipid theories of anesthesia implicate perturbation of membrane lipids as the locus for acute anesthetic action. [1] Chronic exposure to alcohols and anesthetics induces an adaptive response in membrane phospholipids that confers resistance to many of the acute actions of alcohols and anesthetics. [2] We have proposed a colligative thermodynamic reformulation of the Meyer-Overton hypothesis for anesthetic action. [3,4] This reformulation implicates configurational entropy (Scf), the entropy imparted by a solute upon a membrane structure in the partitioning process, as the driving force of solute action on cooperative membrane equilibria. Solute potency is determined by the competing contributions of configurational and thermal entropy (ASt). Equilibria most susceptible to solute action (where dilute concentrations of solutes induce a perturbation equivalent to a large change in temperature) involve large changes in configurational entropy and small changes in thermal entropy according to the following relation. [3]