title: Atomistic study of lipid membranes containing chloroform: looking for a lipid-mediated mechanism of anesthesia.
abstract: The molecular mechanism of general anesthesia is still a controversial issue. Direct effect by linking of anesthetics to proteins and indirect action on the lipid membrane properties are the two hypotheses in conflict. Atomistic simulations of different lipid membranes subjected to the effect of small volatile organohalogen compounds are used to explore plausible lipid-mediated mechanisms. Simulations of homogeneous membranes reveal that electrostatic potential and lateral pressure transversal profiles are affected differently by chloroform (anesthetic) and carbon tetrachloride (non-anesthetic). Simulations of structured membranes that combine ordered and disordered regions show that chloroform molecules accumulate preferentially in highly disordered lipid domains, suggesting that the combination of both lateral and transversal partitioning of chloroform in the cell membrane could be responsible of its anesthetic action.
authors.affiliation: Departament de Química Física and Institut de Química Teòrica i Computacional, Universitat de Barcelona, Barcelona, Spain. reigada@ub.edu
authors.forename: Ramon
authors.initials: R
authors.lastname: Reigada
mesh_terms: D000758:Anesthesia / Q000379:methods*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002725:Chloroform / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D004563:Electrochemistry / Q000379:methods; D006219:Halogens / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry; D008566:Membranes / Q000378:metabolism*; D009930:Organic Chemicals / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D006219:Halogens; D008051:Lipid Bilayers; D008563:Membrane Lipids; D009930:Organic Chemicals; D010713:Phosphatidylcholines; D002725:Chloroform; D002251:Carbon Tetrachloride; C017251:1,2-oleoylphosphatidylcholine