title: Klotho sensitivity of the hERG channel.
abstract: Klotho, a hormone and enzyme, is a powerful regulator of ageing and life span. Klotho deficiency leads to cardiac arrythmia and sudden cardiac death. We thus explored whether klotho modifies cardiac K(+)-channel hERG. Current was determined utilizing dual electrode voltage clamp and hERG protein abundance utilizing immunohistochemistry and chemiluminescence in Xenopus oocytes expressing hERG with or without klotho. Coexpression of klotho increased cell membrane hERG-protein abundance and hERG current at any given voltage without significantly modifying the voltage required to activate the channel. The effect of klotho coexpression was mimicked by recombinant klotho protein and reversed by β-glucuronidase-inhibitor D-saccharic acid-1,4-lactone.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Pakladok
authors.forename: Ahmad
authors.initials: A
authors.lastname: Almilaji
authors.forename: Bernat
authors.initials: B
authors.lastname: Elvira
authors.forename: Guiscard
authors.initials: G
authors.lastname: Seebohm
authors.forename: Jakob
authors.initials: J
authors.lastname: Voelkl
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology*; D005937:Glucaric Acid / Q000494:pharmacology; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015640:Ion Channel Gating; D000090265:Klotho Proteins; D007783:Lactones / Q000494:pharmacology; D008564:Membrane Potentials; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D018075:RNA, Complementary / Q000235:genetics; D014981:Xenopus
chemical_list: C571832:D-Glucaric acid, 1,4-lactone; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007783:Lactones; D018075:RNA, Complementary; D005966:Glucuronidase; D000090265:Klotho Proteins; D005937:Glucaric Acid