title: Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II.
abstract: Polypeptide neurotoxins alter ion channel gating by binding to extracellular receptor sites, even though the voltage sensors are in their S4 transmembrane segments. By analysis of sodium channel chimeras, a beta-scorpion toxin is shown here to negatively shift voltage dependence of activation and enhance closed state inactivation by binding to a receptor site that requires glycine 845 (Gly-845) in the S3-S4 loop at the extracellular end of the S4 segment in domain II of the alpha subunit. Toxin action requires prior depolarization to drive the S4 voltage sensors outward, but these effects are lost in the mutant G845N. The results reveal a voltage sensor-trapping model of toxin action in which the IIS4 voltage sensor is trapped in its outward, activated position by toxin binding.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle 98195, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cestèle
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.forename: J C
authors.initials: JC
authors.lastname: Rogers
authors.forename: H
authors.initials: H
authors.lastname: Rochat
authors.forename: T
authors.initials: T
authors.lastname: Scheuer
authors.forename: W A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002678:Chimera / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D009154:Mutation / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism* / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
chemical_list: C115646:CSS IV toxin; D012604:Scorpion Venoms; D015222:Sodium Channels