title: Nonhalogenated alkane anesthetics fail to potentiate agonist actions on two ligand-gated ion channels.
abstract: BACKGROUND
  Although ether, alcohol, and halogenated alkane anesthetics potentiate agonist actions or increase the apparent agonist affinity of ligand-gated ion channels at clinically relevant concentrations, the effects of nonhalogenated alkane anesthetics on ligand-gated ion channels have not been studied. The current study assessed the abilities of two representative nonhalogenated alkane anesthetics (cyclopropane and butane) to potentiate agonist actions or increase the apparent agonist affinity of two representative ligand-gated ion channels: the nicotinic acetylcholine receptor and y-aminobutyric acid type A (GABA(A)) receptor.
  
  
  METHODS
  Nicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana, and human GABA(A) receptors (alpha1beta2gamma2L) were expressed in human embryonic kidney 293 cells. The Torpedo nicotinic acetylcholine receptors apparent agonist affinity in the presence and absence of anesthetic was assessed by measuring the apparent rates of desensitization induced by a range of acetylcholine concentrations. The GABA(A) receptor's apparent agonist affinity in the presence and absence of anesthetic was assessed by measuring the peak currents induced by a range of GABA concentrations.
  
  
  RESULTS
  Neither cyclopropane nor butane potentiated agonist actions or increased the apparent agonist affinity (reduced the apparent agonist dissociation constant) of the Torpedo nicotinic acetylcholine receptor or GABA(A) receptor. At clinically relevant concentrations, cyclopropane and butane reduced the apparent rate of Torpedo nicotinic acetylcholine receptor desensitization induced by low concentrations of agonist.
  
  
  CONCLUSIONS
  Our results suggest that the in vivo central nervous system depressant effects of nonhalogenated alkane anesthetics do not result from their abilities to potentiate agonist actions on ligand-gated ion channels. Other targets or mechanisms more likely account for the anesthetic activities of nonhalogenated alkane anesthetics.
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA. DRaines@partners.org
authors.forename: D E
authors.initials: DE
authors.lastname: Raines
authors.forename: R J
authors.initials: RJ
authors.lastname: Claycomb
authors.forename: M
authors.initials: M
authors.lastname: Scheller
authors.forename: S A
authors.initials: SA
authors.lastname: Forman
mesh_terms: D000465:Algorithms; D000473:Alkanes / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008024:Ligands; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014101:Torpedo; D014162:Transfection
chemical_list: D000473:Alkanes; D018685:Anesthetics, Inhalation; D008024:Ligands; D018722:Nicotinic Agonists; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic