Ion Channel Regulation by the LKB1-AMPK Signalling Pathway: The Key to Carotid Body Activation by Hypoxia and Metabolic Homeostasis at the Whole Body Level

A. Mark Evans (Lead / Corresponding author), Chris Peers, Christopher N. Wyatt, Prem Kumar, D Grahame Hardie

    Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

    10 Citations (Scopus)

    Abstract

    Our recent investigations provide further support for the proposal that, consequent to inhibition of mitochondrial oxidative phosphorylation, activation of AMP-activated protein kinase (AMPK) mediates carotid body excitation by hypoxia. Consistent with the effects of hypoxia, intracellular dialysis from a patch pipette of an active (thiophosphorylated) recombinant AMPK heterotrimer (α2β2γ1) or application of the AMPK activators AICAR and A769662: (1) Inhibited BK(Ca) currents and TASK K(+) currents in rat carotid body type I cells; (2) Inhibited whole-cell currents carried by KCa1.1 and TASK3, but not TASK1 channels expressed in HEK293 cells; (3) Triggered carotid body activation. Furthermore, preliminary studies using mice with conditional knockout in type I cells of the primary upstream kinase that activates AMPK in response to metabolic stresses, LKB1, appear to confirm our working hypothesis. Studies on mice with knockout of the catalytic α1 subunit and α2 subunits of AMPK, respectively, have proved equally consistent. Accumulating evidence therefore suggests that the LKB1-AMPK signalling pathway is necessary for hypoxia-response coupling by the carotid body, and serves to regulate oxygen and therefore energy supply at the whole body level.

    Original languageEnglish
    Title of host publicationArterial Chemoreception
    Subtitle of host publicationFrom Molecules to Systems
    EditorsColin A. Nurse, Constancio Gonzalez, Chris Peers, Nanduri Prabhakar
    PublisherSpringer
    Pages81-90
    Number of pages10
    Volume758
    ISBN (Electronic) 9789400745841
    ISBN (Print) 9789400745834
    DOIs
    Publication statusPublished - 2012

    Publication series

    NameAdvances in Experimental Medicine and Biology
    PublisherSpringer
    Volume758
    ISSN (Electronic)0065-2598

    Keywords

    • AMP-Activated Protein Kinases
    • Animals
    • Carotid Body
    • Homeostasis
    • Humans
    • Hypoxia
    • Nerve Tissue Proteins
    • Potassium Channels
    • Potassium Channels, Tandem Pore Domain
    • Protein-Serine-Threonine Kinases
    • Signal Transduction
    • Journal Article
    • Research Support, Non-U.S. Gov't
    • Review

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  • Cite this

    Evans, A. M., Peers, C., Wyatt, C. N., Kumar, P., & Hardie, D. G. (2012). Ion Channel Regulation by the LKB1-AMPK Signalling Pathway: The Key to Carotid Body Activation by Hypoxia and Metabolic Homeostasis at the Whole Body Level. In C. A. Nurse, C. Gonzalez, C. Peers, & N. Prabhakar (Eds.), Arterial Chemoreception: From Molecules to Systems (Vol. 758, pp. 81-90). (Advances in Experimental Medicine and Biology; Vol. 758). Springer . https://doi.org/10.1007/978-94-007-4584-1_11