title: Multiple inhibitory actions of lidocaine on Torpedo nicotinic acetylcholine receptors transplanted to Xenopus oocytes.
abstract: Lidocaine is a local anaesthetic that blocks sodium channels, but also inhibits several ligand-gated ion-channels. The aim of this work was to unravel the mechanisms by which lidocaine blocks Torpedo nicotinic receptors transplanted to Xenopus oocytes. Acetylcholine-elicited currents were reversibly blocked by lidocaine, in a concentration dependent manner. At doses lower than the IC(50) , lidocaine blocked nicotinic receptors only at negative potentials, indicating an open-channel blockade; the binding site within the channel was at about 30% of the way through the electrical field across the membrane. In the presence of higher lidocaine doses, nicotinic receptors were blocked both at positive and negative potentials, acetylcholine dose-response curve shifted to the right and lidocaine pre-application, before its co-application with acetylcholine, enhanced the current inhibition, indicating all together that lidocaine also blocked resting receptors; besides, it increased the current decay rate. When lidocaine, at low doses, was co-applied with 2-(triethylammonio)-N-(2,6-dimethylphenyl) acetamide bromide, edrophonium or 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide, which are quaternary-ammonium molecules that also blocked nicotinic receptors, there was an additive inhibitory effect, indicating that these molecules bound to different sites within the channel pore. These results prove that lidocaine blocks nicotinic receptors by several independent mechanisms and evidence the diverse and complex modulation of this receptor by structurally related molecules.
authors.affiliation: División de Fisiología, Dpto. de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain.
authors.forename: Armando
authors.initials: A
authors.lastname: Alberola-Die
authors.forename: Juan
authors.initials: J
authors.lastname: Martinez-Pinna
authors.forename: José Manuel
authors.initials: JM
authors.lastname: González-Ros
authors.forename: Isabel
authors.initials: I
authors.lastname: Ivorra
authors.forename: Andrés
authors.initials: A
authors.lastname: Morales
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004491:Edrophonium / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology*; D014101:Torpedo; D014982:Xenopus laevis
chemical_list: D000779:Anesthetics, Local; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C012647:QX-314; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide; D004491:Edrophonium; D008012:Lidocaine; D000109:Acetylcholine