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• W2476674920 abstract "Key points Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (K v ) in pulmonary arterial smooth muscle by hypoxia, although the precise molecular mechanisms have been unclear. AMP‐activated protein kinase (AMPK) has been proposed to couple inhibition of mitochondrial metabolism by hypoxia to acute hypoxic pulmonary vasoconstriction and progression of pulmonary hypertension. Inhibition of complex I of the mitochondrial electron transport chain activated AMPK and inhibited K v 1.5 channels in pulmonary arterial myocytes. AMPK activation by 5‐aminoimidazole‐4‐carboxamide riboside, A769662 or C13 attenuated K v 1.5 currents in pulmonary arterial myocytes, and this effect was non‐additive with respect to K v 1.5 inhibition by hypoxia and mitochondrial poisons. Recombinant AMPK phosphorylated recombinant human K v 1.5 channels in cell‐free assays, and inhibited K + currents when introduced into HEK 293 cells stably expressing K v 1.5. These results suggest that AMPK is the primary mediator of reductions in K v 1.5 channels following inhibition of mitochondrial oxidative phosphorylation during hypoxia and by mitochondrial poisons. Abstract Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (K v ) in pulmonary arterial smooth muscle cells that is mediated by the inhibition of mitochondrial oxidative phosphorylation. We sought to determine the role in this process of the AMP‐activated protein kinase (AMPK), which is intimately coupled to mitochondrial function due to its activation by LKB1‐dependent phosphorylation in response to increases in the cellular AMP:ATP and/or ADP:ATP ratios. Inhibition of complex I of the mitochondrial electron transport chain using phenformin activated AMPK and inhibited K v currents in pulmonary arterial myocytes, consistent with previously reported effects of mitochondrial inhibitors. Myocyte K v currents were also markedly inhibited upon AMPK activation by A769662, 5‐aminoimidazole‐4‐carboxamide riboside and C13 and by intracellular dialysis from a patch‐pipette of activated (thiophosphorylated) recombinant AMPK heterotrimers (α2β2γ1 or α1β1γ1). Hypoxia and inhibitors of mitochondrial oxidative phosphorylation reduced AMPK‐sensitive K + currents, which were also blocked by the selective K v 1.5 channel inhibitor diphenyl phosphine oxide‐1 but unaffected by the presence of the BK Ca channel blocker paxilline. Moreover, recombinant human K v 1.5 channels were phosphorylated by AMPK in cell‐free assays, and K + currents carried by K v 1.5 stably expressed in HEK 293 cells were inhibited by intracellular dialysis of AMPK heterotrimers and by A769662, the effects of which were blocked by compound C. We conclude that AMPK mediates K v channel inhibition by hypoxia in pulmonary arterial myocytes, at least in part, through phosphorylation of K v 1.5 and/or an associated protein." @default.
• W2476674920 created "2016-08-23" @default.
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• W2476674920 date "2016-06-30" @default.
• W2476674920 modified "2023-10-03" @default.
• W2476674920 title "AMP-activated protein kinase inhibits K_v1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation" @default.
• W2476674920 cites W1492054762 @default.
• W2476674920 cites W1964285407 @default.
• W2476674920 cites W1965927487 @default.
• W2476674920 cites W1966316646 @default.
• W2476674920 cites W1966706887 @default.
• W2476674920 cites W1968881729 @default.
• W2476674920 cites W1969151861 @default.
• W2476674920 cites W1970467935 @default.
• W2476674920 cites W1979000812 @default.
• W2476674920 cites W1995069275 @default.
• W2476674920 cites W1995272882 @default.
• W2476674920 cites W2009268839 @default.
• W2476674920 cites W2014511124 @default.
• W2476674920 cites W2015924396 @default.
• W2476674920 cites W2019206423 @default.
• W2476674920 cites W2020255363 @default.
• W2476674920 cites W2030884210 @default.
• W2476674920 cites W2031765503 @default.
• W2476674920 cites W2032065353 @default.
• W2476674920 cites W2038163496 @default.
• W2476674920 cites W2039212784 @default.
• W2476674920 cites W2041234387 @default.
• W2476674920 cites W2043129303 @default.
• W2476674920 cites W2046027041 @default.
• W2476674920 cites W2046822015 @default.
• W2476674920 cites W2050099786 @default.
• W2476674920 cites W2050427373 @default.
• W2476674920 cites W2052458266 @default.
• W2476674920 cites W2052716105 @default.
• W2476674920 cites W2055415244 @default.
• W2476674920 cites W2057998788 @default.
• W2476674920 cites W2060510646 @default.
• W2476674920 cites W2063665010 @default.
• W2476674920 cites W2068027702 @default.
• W2476674920 cites W2080481362 @default.
• W2476674920 cites W2083655799 @default.
• W2476674920 cites W2085516423 @default.
• W2476674920 cites W2086204033 @default.
• W2476674920 cites W2090192743 @default.
• W2476674920 cites W2091469763 @default.
• W2476674920 cites W2091965408 @default.
• W2476674920 cites W2098038478 @default.
• W2476674920 cites W2101351673 @default.
• W2476674920 cites W2103659405 @default.
• W2476674920 cites W2103851013 @default.
• W2476674920 cites W2105109509 @default.
• W2476674920 cites W2105828748 @default.
• W2476674920 cites W2107922680 @default.
• W2476674920 cites W2113166898 @default.
• W2476674920 cites W2117275311 @default.
• W2476674920 cites W2117692193 @default.
• W2476674920 cites W2119953180 @default.
• W2476674920 cites W2120189207 @default.
• W2476674920 cites W2131264643 @default.
• W2476674920 cites W2135875385 @default.
• W2476674920 cites W2138951322 @default.
• W2476674920 cites W2140377941 @default.
• W2476674920 cites W2147086583 @default.
• W2476674920 cites W2147750581 @default.
• W2476674920 cites W2149483660 @default.
• W2476674920 cites W2151260260 @default.
• W2476674920 cites W2151344601 @default.
• W2476674920 cites W2152373667 @default.
• W2476674920 cites W2154366496 @default.
• W2476674920 cites W2158364013 @default.
• W2476674920 cites W2159649507 @default.
• W2476674920 cites W2160103929 @default.
• W2476674920 cites W2161146119 @default.
• W2476674920 cites W2161780042 @default.
• W2476674920 cites W2162794459 @default.
• W2476674920 cites W2163721144 @default.
• W2476674920 cites W2164474183 @default.
• W2476674920 cites W2165928579 @default.
• W2476674920 cites W2166985476 @default.
• W2476674920 cites W2168503405 @default.
• W2476674920 cites W2174118934 @default.
• W2476674920 cites W2181344473 @default.
• W2476674920 cites W2188714410 @default.
• W2476674920 cites W2311570504 @default.
• W2476674920 cites W2387856814 @default.
• W2476674920 doi "https://doi.org/10.1113/jp272032" @default.
• W2476674920 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5009768" @default.
• W2476674920 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27062501" @default.
• W2476674920 hasPublicationYear "2016" @default.
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