The effect of general anesthetics on the dynamics of phosphatidylcholine-acetylcholine receptor interactions in reconstituted vesicles

Biochim Biophys Acta. 1993 Apr 8;1147(1):143-53. doi: 10.1016/0005-2736(93)90325-t.


The interaction of general anesthetics at the lipid/protein interface of the nicotinic acetylcholine receptor reconstituted in dioleoylphosphatidylcholine bilayers at various lipid/protein ratios has been studied using the electron spin resonance spectra of phosphatidylcholine spin-labeled at the fourteenth acyl carbon (14-PCSL). In addition to the bilayer spectrum, the spin label reported a more motionally restricted environment whose contribution increased with increasing protein/lipid ratio. Exchange between these two environments occurred at a rate of approx. 6 x 10(7) s-1. The motionally restricted, protein-associated 14-PCSL had a rotational correlation time of about 10-20 ns, an order of magnitude slower than when in the bilayer. Addition of 1-hexanol (up to 16 mM) to the reconstituted receptor perturbed the acyl chains of the bulk lipid phase, but the motional properties of the lipid acyl chains at the protein/lipid interface near the membrane center were not significantly perturbed on the EPR motional time-scale. Similarly, anesthetics that were less effective at perturbing the bilayer, such as pentobarbital (up to 2 mM) and isoflurane (7 mM), did not perturb the lipid/protein interface on the conventional EPR motional time scale.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anesthesia, General
  • Anesthetics / pharmacology*
  • Animals
  • Hexanols / pharmacology
  • Lipid Bilayers / metabolism*
  • Phosphatidylcholines / metabolism*
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Torpedo


  • Anesthetics
  • Hexanols
  • Lipid Bilayers
  • Phosphatidylcholines
  • Receptors, Nicotinic
  • 1-hexanol
  • 1,2-oleoylphosphatidylcholine