Modulation of O2 Sensitive K+ Channels by AMP-Activated Protein Kinase

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Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chemotransduction. We have recently suggested that hypoxic channel inhibition is mediated by AMP-activated protein kinase (AMPK). Here, we have further explored the modulation by AMPK of recombinant K+ channels (expressed in HEK293 cells) whose native counterparts are considered O2-sensitive in the rat carotid body. Inhibition of maxiK channels by AMPK activation with AICAR was found to be independent of [Ca2+]i and occurred regardless of whether the α subunit was co-expressed with an auxiliary β subunit. All effects of AICAR were fully reversed by the AMPK inhibitor compound C. MaxiK channels were also inhibited by the novel AMPK activator A-769662 and by intracellular dialysis with the constitutively active, truncated AMPK mutant, T172D. The molecular identity of the O2-sensitive leak K+ conductance in rat type I cells remains unclear, but shares similarities with TASK-1 and TASK-3. Recombinant TASK-1 was insensitive to AICAR. However, TASK-3 was inhibited by either AICAR or A-769662 in a manner which was reversed by compound C. These data highlight a role for AMPK in the modulation of two proposed O2 sensitive K+ channels found in the carotid body.


Presented at the 17th International Society for Arterial Chemoreception (ISAC) Meeting, Valladolid, Spain.



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