title: Identification and characterization of anesthetic targets by mouse molecular genetics approaches.
abstract: OBJECTIVE
  It is now generally accepted that proteins are the primary targets of general anesthetics. However, the demonstration that the activity of a protein is altered by general anesthetics at clinically relevant concentrations in vitro does not provide direct evidence that this target mediates pharmacological actions of general anesthetics. Here we report on advances that have been made in identifying the contribution of individual ligand-gated ion channels to defined anesthetic endpoints using molecular mouse genetics.
  
  
  RESULTS
  Gamma-aminobutyric acid (GABA)(A) receptor subtypes defined by the presence of the α1, α4, α5, β2, and β3 subunits and two-pore domain potassium channels (TASK-1, TASK-3, and TREK) have been discovered to mediate, at least in part, the hypnotic, immobilizing or amnestic actions of intravenous and volatile general anesthetics. Moreover, using tissues from genetically modified mice, specific functions of GABA(A) receptor subtypes in cortical and spinal neuronal networks were identified.
  
  
  CONCLUSIONS
  Genetically modified mice have been very useful for research on mechanisms of anesthesia and have contributed to the functional identification of general anesthetic targets and of the role of these targets in neuronal networks.
authors.affiliation: Section of Experimental Anaesthesiology, Department of Anaesthesiology, Eberhard-Karls-University, Tuebingen, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Drexler
authors.forename: Bernd
authors.initials: B
authors.lastname: Antkowiak
authors.forename: Elif
authors.initials: E
authors.lastname: Engin
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
mesh_terms: D000768:Anesthesia, General / Q000379:methods; D018681:Anesthetics, General / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D058446:Ligand-Gated Ion Channels / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008967:Molecular Biology / Q000379:methods; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D018681:Anesthetics, General; D058446:Ligand-Gated Ion Channels; D011963:Receptors, GABA-A