Ion Channel Regulation by AMPK

Autor: Mark L. Dallas, D. Grahame Hardie, Christopher N. Wyatt, Benoit Viollet, Oluseye A. Ogunbayo, Heidi L. Jordan, Barbara L. Barr, Naoko Ikematsu, A. Mark Evans, Prem Kumar, Fiona A. Ross, Chris Peers, J. Nicole Rafferty
Rok vydání: 2009
Předmět:
Zdroj: Annals of the New York Academy of Sciences. 1177:89-100
ISSN: 0077-8923
DOI: 10.1111/j.1749-6632.2009.05041.x
Popis: Vital homeostatic mechanisms monitor O2 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 O2 deficit to those rich in O2, while a fall in arterial pO2 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 O2 and thereby energy (ATP) supply at the whole body as well as the cellular level.
Databáze: OpenAIRE
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