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.
Available at: http://works.bepress.com/christopher_wyatt/52/