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PKC and AMPK regulation of Kv1.5 potassium channels
Authors:Martin Nybo Andersen  Lasse Skibsbye  Chuyi Tang  Frederic Petersen  Nanna MacAulay  Hanne Borger Rasmussen  Thomas Jespersen
Institution:Danish National Research Foundation Center for Cardiac Arrhythmia; Dept. of Biomedical Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen, Denmark
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.
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