This preclinical study demonstrates that Kv1.5 potassium channels are regulated by PKC and AMPK kinases through distinct molecular mechanisms depending on the cell system.
Kv1.5 regulation by PKC and AMPK is cell-context dependent; leaves open therapeutic targeting in atrial arrhythmias pending mammalian validation.
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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Andersen et al. (2015) studied this question.
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