title: Alpha subunit isoform influences GABA(A) receptor modulation by propofol.
abstract: We have investigated the role of the alpha subunit in the modulation of gamma-aminobutyric acid type A (GABA(A)) receptors by the general anesthetic propofol, using whole-cell patch clamp recordings made from distinct stable fibroblast cell lines which expressed only alpha1beta3gamma2 or alpha6beta3gamma2 GABA(A) receptors. At clinically relevant anesthetic concentrations, propofol potentiated submaximal GABA currents in alpha1beta3gamma2 receptors to a far greater degree than those in alpha6beta3gamma2 receptors. The alpha subunit influenced the efficacy of propofol for modulation, but not its potency. In contrast, direct gating of the ion channel by propofol, in the absence of GABA, was significantly larger in the alpha6 than the alpha1 containing receptors. The potentiation of submaximal GABA by trichloroethanol, and the potentiation and direct gating by methohexital was also studied, and showed the same relative trends as propofol.
authors.affiliation: Department of Anesthesia and Critical Care, University of Chicago, IL 60637, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Krasowski
authors.forename: S M
authors.initials: SM
authors.lastname: O'Shea
authors.forename: C E
authors.initials: CE
authors.lastname: Rick
authors.forename: P J
authors.initials: PJ
authors.lastname: Whiting
authors.forename: K L
authors.initials: KL
authors.lastname: Hadingham
authors.forename: C
authors.initials: C
authors.lastname: Czajkowski
authors.forename: N L
authors.initials: NL
authors.lastname: Harrison
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives / Q000494:pharmacology; D008723:Methohexital / Q000494:pharmacology; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013237:Stereoisomerism
chemical_list: D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D009118:Muscimol; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol; D008723:Methohexital; D015742:Propofol