Ion Channel Regulation by AMPK: The Route of Hypoxia-Response Coupling in the Carotid Body and Pulmonary Artery

A. Mark Evans, D. Grahame Hardie, Chris Peers, Christopher N. Wyatt, Benoit Viollet, Prem Kumar, Mark L. Dallas, Fiona Ross, Naoko Ikematsu, Heidi L. Jordan, Barbara L. Barr, J. Nicole Rafferty, Oluseye Ogunbayo

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

    31 Citations (Scopus)

    Abstract

    Vital homeostatic mechanisms monitor O-2 supply and adjust respiratory and circulatory function to meet demand. The pulmonary arteries and carotid bodies are key systems in this respect. Hypoxic pulmonary vasoconstriction (HPV) aids ventilation-perfusion matching in the lung by diverting blood flow from areas with an O-2 deficit to those rich in O-2, while a fall in arterial pO(2) increases sensory afferent discharge from the carotid body to elicit corrective changes in breathing patterns. We discuss here the new concept that hypoxia, by inhibiting oxidative phosphorylation, activates AMP-activated protein kinase (AMPK) leading to consequent phosphorylation of target proteins, such as ion channels, which initiate pulmonary artery constriction and carotid body activation. Consistent with this view, AMPK knockout mice exhibit an impaired ventilatory response to hypoxia. Thus, AMPK may be sufficient and necessary for hypoxia-response coupling and may regulate O-2 and thereby energy (ATP) supply at the whole body as well as the cellular level.

    Original languageEnglish
    Title of host publicationHypoxia and Consequences From Molecule to Malady
    EditorsC. Peers, G. G. Haddad, N. S. Chandel
    Place of PublicationOxford
    PublisherBlackwell
    Pages89-100
    Number of pages12
    ISBN (Print)9781573317733
    DOIs
    Publication statusPublished - 2009
    EventConference on Hypoxia and Consequences - From Molecule to Malady - New York, United States
    Duration: 12 Mar 200914 Mar 2009

    Publication series

    NameAnnals of the New York Academy of Sciences
    Volume1177

    Conference

    ConferenceConference on Hypoxia and Consequences - From Molecule to Malady
    CountryUnited States
    CityNew York
    Period12/03/0914/03/09

    Keywords

    • AMP-activated protein kinase (AMPK)
    • hypoxia
    • calcium
    • carotid body
    • pulmonary artery
    • hypoxic pulmonary vasoconstriction (HPV)
    • ACTIVATED PROTEIN-KINASE
    • CYCLIC ADP-RIBOSE
    • ADRENOMEDULLARY CHROMAFFIN CELLS
    • SMOOTH-MUSCLE-CELLS
    • CHEMORECEPTOR CELLS
    • K+ CURRENT
    • I CELLS
    • GLUCOSE-TRANSPORT
    • O-2-SENSING CELLS
    • ENERGY

    Cite this

    Evans, A. M., Hardie, D. G., Peers, C., Wyatt, C. N., Viollet, B., Kumar, P., Dallas, M. L., Ross, F., Ikematsu, N., Jordan, H. L., Barr, B. L., Rafferty, J. N., & Ogunbayo, O. (2009). Ion Channel Regulation by AMPK: The Route of Hypoxia-Response Coupling in the Carotid Body and Pulmonary Artery. In C. Peers, G. G. Haddad, & N. S. Chandel (Eds.), Hypoxia and Consequences From Molecule to Malady (pp. 89-100). (Annals of the New York Academy of Sciences; Vol. 1177). Blackwell. https://doi.org/10.1111/j.1749-6632.2009.05041.x