title: GABA(A) receptor activation and open-channel block by volatile anaesthetics: a new principle of receptor modulation?
abstract: The rapid application of solutions containing the volatile anaesthetics isoflurane or sevoflurane induced inward currents in human embryonic kidney (HEK293) cells carrying rat recombinant alpha(1)beta(2)gamma(2L) GABA(A) receptor assemblies. The responses evoked by the anaesthetics applied via a fast delivery system were recorded using the patch-clamp technique in the whole-cell mode. The anaesthetics induced a fast inward current which was followed by a prominent tail current upon the rapid withdrawal of the agent. These currents were simulated using a kinetic scheme embodying two agonist-like binding steps required for receptor activation, and one binding step by which the anaesthetic induces an open-channel block. According to this model of a biphasic receptor modulation, the open-channel block delays the ion flux through the ligand-gated receptors and, thus, prolongs the overall duration of the current response. Open-channel blocks might also be operative in other ligand-gated ion channels to modulate synaptic strength.
authors.affiliation: Department of Anaesthesiology, Technische Universität München, Ismaninger Str 22, 81675 Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haseneder
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rammes
authors.forename: Walter
authors.initials: W
authors.lastname: Zieglgänsberger
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kochs
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hapfelmeier
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D011963:Receptors, GABA-A; D000077149:Sevoflurane; D007530:Isoflurane