Ion channel regulation by AMPK: the route of hypoxia-response coupling in thecarotid body and pulmonary artery.
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.
Evans
A Mark
AM
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom. mark.evans@ed.ac.uk
Hardie
D Grahame
DG
Peers
Chris
C
Wyatt
Christopher N
CN
Viollet
Benoit
B
Kumar
Prem
P
Dallas
Mark L
ML
Ross
Fiona
F
Ikematsu
Naoko
N
Jordan
Heidi L
HL
Barr
Barbara L
BL
Rafferty
J Nicole
JN
Ogunbayo
Oluseye
O
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011651:Pulmonary Artery / Q000378:metabolism*
D007473:Ion Channels; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases