title: Molecular basis of IsK protein regulation by oxidation or chelation.
abstract: Slowly activating IsK channels were expressed in Xenopus oocytes and exposed to oxidative agents. Oxidative treatment reduced the resulting current IsK, while no inhibition was observed for IsK protein mutants carrying a Ser mutation instead of a highly conserved Cys residue in the intracellular domain. In contrast, Hg2+, which may not only oxidize thiol groups but also form chelates with dibasic amino acids, caused a use-dependent, positive regulation of IsK. This effect was reversed in an IsK protein mutant with a deletion in the extracellular domain. These data suggest opposite effects of peroxides and Hg2+ on IsK, a peroxide-mediated IsK inhibition by intracellular oxidation and a Hg(2+)-mediated IsK increase, caused by extracellular Hg2+ chelation of the IsK protein.
authors.affiliation: Physiological Institute I, University of Tübingen, Federal Republic of Germany.
authors.forename: A E
authors.initials: AE
authors.lastname: Busch
authors.forename: S
authors.initials: S
authors.lastname: Waldegger
authors.forename: T
authors.initials: T
authors.lastname: Herzer
authors.forename: G
authors.initials: G
authors.lastname: Raber
authors.forename: E
authors.initials: E
authors.lastname: Gulbins
authors.forename: T
authors.initials: T
authors.lastname: Takumi
authors.forename: K
authors.initials: K
authors.lastname: Moriyoshi
authors.forename: S
authors.initials: S
authors.lastname: Nakanishi
authors.forename: F
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002614:Chelating Agents; D006801:Humans; D008628:Mercury / Q000737:chemistry; D009154:Mutation; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017384:Sequence Deletion; D014982:Xenopus laevis
chemical_list: D002614:Chelating Agents; D016877:Oxidants; D010545:Peroxides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); D008628:Mercury