Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase

M. L. Dallas, J. L. Scragg, C. N. Wyatt, F. Ross, D. G. Hardie, A. M. Evans, C. Peers

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    18 Citations (Scopus)

    Abstract

    Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chernotransduction. We have recently suggested that hypoxic channel inhibition is mediated by AMP-activated protein kinase (AMPK). Here, we have further explored the modulation by AMPK of recombinant K+ channels (expressed in HEK293 cells) whose native counterparts are considered O-2-sensitive in the rat carotid body. Inhibition of maxiK channels by AMPK activation with AICAR was found to be independent of [Ca2+](i) and occurred regardless of whether the alpha subunit was co-expressed with an auxiliary beta subunit. All effects of AICAR were fully reversed by the AMPK inhibitor compound C. MaxiK channels were also inhibited by the novel AMPK activator A-769662 and by intracellular dialysis with the constitutively active, truncated AMPK mutant, T172D. The molecular identity of the O-2-sensitive leak K+ conductance in rat type I cells remains unclear, but shares similarities with TASK-1 and TASK-3. Recombinant TASK-I was insensitive to AICAR. However, TASK-3 was inhibited by either AICAR or A-769662 in a manner which was reversed by compound C. These data highlight a role for AMPK in the modulation of two proposed O-2 sensitive K+ channels found in the carotid body.

    Original languageEnglish
    Title of host publicationArterial Chemoreceptors
    EditorsC. Gonzalez, C. A. Nurse, C. Peers
    Place of PublicationBERLIN
    PublisherSpringer
    Pages57-63
    Number of pages7
    ISBN (Print)9789048122585
    DOIs
    Publication statusPublished - 2009
    Event17th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC) - Valladolid, Spain
    Duration: 1 Jul 20085 Jul 2008

    Publication series

    NameAdvances in Experimental Medicine and Biology
    Volume648

    Conference

    Conference17th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC)
    CountrySpain
    CityValladolid
    Period1/07/085/07/08

    Keywords

    • K+ channel
    • Hypoxia
    • AMP kinase
    • maxiK channel
    • Leak K+ channel
    • TASK channel
    • Patch clamp
    • CAROTID-BODY EXCITATION
    • CELLS
    • HYPOXIA
    • SUBUNITS

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