title: Gambierol and n-alkanols inhibit Shaker Kv channel via distinct binding sites outside the K(+) pore.
abstract: The marine polycyclic-ether toxin gambierol and 1-butanol (n-alkanol) inhibit Shaker-type Kv channels by interfering with the gating machinery. Competition experiments indicated that both compounds do not share an overlapping binding site but gambierol is able to affect 1-butanol affinity for Shaker through an allosteric effect. Furthermore, the Shaker-P475A mutant, which inverses 1-butanol effect, is inhibited by gambierol with nM affinity. Thus, gambierol and 1-butanol inhibit Shaker-type Kv channels via distinct parts of the gating machinery.
authors.affiliation: Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Martínez-Morales
authors.affiliation: Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kopljar
authors.affiliation: Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, UT 84112-0850, USA.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Rainier
authors.affiliation: Toxicology & Pharmacology, Campus Gasthuisberg, Onderwijs en Navorsing 2, Herestraat 49, bus 922, KULeuven, B-3000, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.affiliation: Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Snyders
authors.affiliation: Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium. Electronic address: alain.labro@uantwerpen.be.
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Labro
mesh_terms: D020001:1-Butanol / Q000633:toxicity*; D001665:Binding Sites; D002922:Ciguatoxins / Q000633:toxicity*; D015640:Ion Channel Gating; D026902:Potassium Channel Blockers / Q000633:toxicity*; D051637:Shaker Superfamily of Potassium Channels / Q000037:antagonists & inhibitors*; D035964:Oxocins
chemical_list: D020001:1-Butanol; D002922:Ciguatoxins; D026902:Potassium Channel Blockers; D051637:Shaker Superfamily of Potassium Channels; C435770:gambierol; D035964:Oxocins
keywords: 1-Alcohol; Electrophysiology; Gating modifier; Lipophilic marine toxin; Potassium channel