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
Document Type
Conference Proceeding
Publication Date
4-2012
Find in a Library
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 (α2β21) or application of the AMPK activators AICAR and A769662: (1) Inhibited BKCa 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 data suggest that either conditional knockout of Lkb1 in type I cells or global knockout of the catalytic α1 and α2 subunit of AMPK, respectively, markedly attenuated the ventilatory response of mice to hypoxia. 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.
Repository Citation
Evans, A. M.,
Hardie, D. G.,
Peers, C.,
Kumar, P.,
& Wyatt, C. N.
(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. The FASEB Journal, 26 (Meeting Abstract Supplement).
https://corescholar.libraries.wright.edu/ncbp/835
Comments
Presented at the 2012 Federation of American Societies for Experimental Biology (FASEB) Science Research Conference, San Diego, CA.
Presentation Number 897.4.