title: The membrane lipid cholesterol modulates anesthetic actions on a human brain ion channel.
abstract: BACKGROUND
  Molecular theories of general anesthesia often are divided into two categories: (1) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.
  
  
  METHODS
  Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.
  
  
  RESULTS
  Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half.
  
  
  CONCLUSIONS
  These results support a critical role for the lipid membrane in some anesthetic actions and further indicate that differences in lipid composition must be considered in the interpretation of results when comparing the anesthetic potencies of potential targets in model systems.
authors.affiliation: Department of Anesthesiology, Cornell University Medical College, New York, New York 10021.
authors.forename: B
authors.initials: B
authors.lastname: Rehberg
authors.forename: B W
authors.initials: BW
authors.lastname: Urban
authors.forename: D S
authors.initials: DS
authors.lastname: Duch
mesh_terms: D002540:Cerebral Cortex / Q000737:chemistry; D002784:Cholesterol / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000502:physiology; D010714:Phosphatidylethanolamines / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects*
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D015222:Sodium Channels; D002784:Cholesterol; D010424:Pentobarbital