Anesthetics reduce the magnitude of the membrane dipole potential. Measurements in lipid vesicles using voltage-sensitive spin probes.

Lipid membranes possess a large internal dipole potential that greatly exceeds the magnitude of typical transmembrane or surface potentials. The volatile general anesthetics, halothane, isoflurane and enflurane were tested by the use of positively and negatively charged hydrophobic ion spin labels in lipid bilayer vesicles for their ability to modulate the membrane dipole potential. These anesthetics decreased the binding of negatively charged hydrophobic ion spin probes based on trinitrophenol, but increased the binding of positively charged hydrophobic ion probes based on triphenylalkylphosphoniums. They also enhanced the transit rates for both hydrophobic anions and cations; however, translocation rates were enhanced to a greater extent for the cation probes compared to the anion probes. The changes in binding constant for cations versus anions could be accurately accounted for using a simple model for the free energy profile for hydrophobic ions across membranes, and indicate that these anesthetics decrease the membrane dipole potential. From a fit of the experimental data to this model, anesthetics could promote a decrease in the dipole potential in two ways. First, anesthetics appear to modify the effective dipole moment in the membrane interface and may accomplish this by orienting their molecular dipole antiparallel to the intrinsic dipoles at the interface. Second, they modify the membrane dielectric constant, leading to a decrease in the field across the interface. At equivalent membrane concentrations, isoflurane, enflurane, and halothane produced similar changes in the dipole potential and decreased the dipole potential as much as 65 mV at a membrane mole fraction of 0.20.(ABSTRACT TRUNCATED AT 250 WORDS)