title: PKC and AMPK regulation of Kv1.5 potassium channels.
abstract: The voltage-gated Kv1.5 potassium channel, conducting the ultra-rapid rectifier K(+) current (IKur), is regulated through several pathways. Here we investigate if Kv1.5 surface expression is controlled by the 2 kinases PKC and AMPK, using Xenopus oocytes, MDCK cells and atrial derived HL-1 cells. By confocal microscopy combined with electrophysiology we demonstrate that PKC activation reduces Kv1.5 current, through a decrease in membrane expressed channels. AMPK activation was found to decrease the membrane expression in MDCK cells, but not in HL-1 cells and was furthermore shown to be dependent on co-expression of Nedd4-2 in Xenopus oocytes. These results indicate that Kv1.5 channels are regulated by both kinases, although through different molecular mechanisms in different cell systems.
authors.affiliation: a Danish National Research Foundation Center for Cardiac Arrhythmia; Dept. of Biomedical Sciences ; Faculty of Health and Medical Sciences; University of Copenhagen ; Copenhagen , Denmark.
authors.forename: Martin Nybo
authors.initials: MN
authors.lastname: Andersen
authors.forename: Lasse
authors.initials: L
authors.lastname: Skibsbye
authors.forename: Chuyi
authors.initials: C
authors.lastname: Tang
authors.forename: Frederic
authors.initials: F
authors.lastname: Petersen
authors.forename: Nanna
authors.initials: N
authors.lastname: MacAulay
authors.forename: Hanne Borger
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Thomas
authors.initials: T
authors.lastname: Jespersen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D004285:Dogs; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D005260:Female; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D000075702:Nedd4 Ubiquitin Protein Ligases; D009865:Oocytes / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D051666:Kv1.5 Potassium Channel; D029867:Xenopus Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618482:Nedd4 protein, Xenopus; C000618460:nedd4l protein, Xenopus; D044767:Ubiquitin-Protein Ligases; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases