Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase

M. L. Dallas, J. L. Scragg, C. N. Wyatt, F. Ross, D. G. Hardie, A. M. Evans, C. Peers

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    18 Citations (Scopus)

    Abstract

    Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chernotransduction. 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 O-2-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 alpha subunit was co-expressed with an auxiliary beta 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 O-2-sensitive leak K+ conductance in rat type I cells remains unclear, but shares similarities with TASK-1 and TASK-3. Recombinant TASK-I 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 O-2 sensitive K+ channels found in the carotid body.

    Original languageEnglish
    Title of host publicationArterial Chemoreceptors
    EditorsC. Gonzalez, C. A. Nurse, C. Peers
    Place of PublicationBERLIN
    PublisherSpringer
    Pages57-63
    Number of pages7
    ISBN (Print)9789048122585
    DOIs
    Publication statusPublished - 2009
    Event17th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC) - Valladolid, Spain
    Duration: 1 Jul 20085 Jul 2008

    Publication series

    NameAdvances in Experimental Medicine and Biology
    Volume648

    Conference

    Conference17th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC)
    CountrySpain
    CityValladolid
    Period1/07/085/07/08

    Keywords

    • K+ channel
    • Hypoxia
    • AMP kinase
    • maxiK channel
    • Leak K+ channel
    • TASK channel
    • Patch clamp
    • CAROTID-BODY EXCITATION
    • CELLS
    • HYPOXIA
    • SUBUNITS

    Cite this

    Dallas, M. L., Scragg, J. L., Wyatt, C. N., Ross, F., Hardie, D. G., Evans, A. M., & Peers, C. (2009). Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase. In C. Gonzalez, C. A. Nurse, & C. Peers (Eds.), Arterial Chemoreceptors (pp. 57-63). (Advances in Experimental Medicine and Biology; Vol. 648). BERLIN: Springer . https://doi.org/10.1007/978-90-481-2259-2_6
    Dallas, M. L. ; Scragg, J. L. ; Wyatt, C. N. ; Ross, F. ; Hardie, D. G. ; Evans, A. M. ; Peers, C. / Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase. Arterial Chemoreceptors. editor / C. Gonzalez ; C. A. Nurse ; C. Peers. BERLIN : Springer , 2009. pp. 57-63 (Advances in Experimental Medicine and Biology).
    @inproceedings{b699653998224e01a7df0b5772e31114,
    title = "Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase",
    abstract = "Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chernotransduction. 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 O-2-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 alpha subunit was co-expressed with an auxiliary beta 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 O-2-sensitive leak K+ conductance in rat type I cells remains unclear, but shares similarities with TASK-1 and TASK-3. Recombinant TASK-I 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 O-2 sensitive K+ channels found in the carotid body.",
    keywords = "K+ channel, Hypoxia, AMP kinase, maxiK channel, Leak K+ channel, TASK channel, Patch clamp, CAROTID-BODY EXCITATION, CELLS, HYPOXIA, SUBUNITS",
    author = "Dallas, {M. L.} and Scragg, {J. L.} and Wyatt, {C. N.} and F. Ross and Hardie, {D. G.} and Evans, {A. M.} and C. Peers",
    year = "2009",
    doi = "10.1007/978-90-481-2259-2_6",
    language = "English",
    isbn = "9789048122585",
    series = "Advances in Experimental Medicine and Biology",
    publisher = "Springer",
    pages = "57--63",
    editor = "C. Gonzalez and Nurse, {C. A.} and C. Peers",
    booktitle = "Arterial Chemoreceptors",

    }

    Dallas, ML, Scragg, JL, Wyatt, CN, Ross, F, Hardie, DG, Evans, AM & Peers, C 2009, Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase. in C Gonzalez, CA Nurse & C Peers (eds), Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol. 648, Springer , BERLIN, pp. 57-63, 17th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC), Valladolid, Spain, 1/07/08. https://doi.org/10.1007/978-90-481-2259-2_6

    Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase. / Dallas, M. L.; Scragg, J. L.; Wyatt, C. N.; Ross, F.; Hardie, D. G.; Evans, A. M.; Peers, C.

    Arterial Chemoreceptors. ed. / C. Gonzalez; C. A. Nurse; C. Peers. BERLIN : Springer , 2009. p. 57-63 (Advances in Experimental Medicine and Biology; Vol. 648).

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    TY - GEN

    T1 - Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase

    AU - Dallas, M. L.

    AU - Scragg, J. L.

    AU - Wyatt, C. N.

    AU - Ross, F.

    AU - Hardie, D. G.

    AU - Evans, A. M.

    AU - Peers, C.

    PY - 2009

    Y1 - 2009

    N2 - Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chernotransduction. 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 O-2-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 alpha subunit was co-expressed with an auxiliary beta 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 O-2-sensitive leak K+ conductance in rat type I cells remains unclear, but shares similarities with TASK-1 and TASK-3. Recombinant TASK-I 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 O-2 sensitive K+ channels found in the carotid body.

    AB - Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chernotransduction. 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 O-2-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 alpha subunit was co-expressed with an auxiliary beta 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 O-2-sensitive leak K+ conductance in rat type I cells remains unclear, but shares similarities with TASK-1 and TASK-3. Recombinant TASK-I 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 O-2 sensitive K+ channels found in the carotid body.

    KW - K+ channel

    KW - Hypoxia

    KW - AMP kinase

    KW - maxiK channel

    KW - Leak K+ channel

    KW - TASK channel

    KW - Patch clamp

    KW - CAROTID-BODY EXCITATION

    KW - CELLS

    KW - HYPOXIA

    KW - SUBUNITS

    U2 - 10.1007/978-90-481-2259-2_6

    DO - 10.1007/978-90-481-2259-2_6

    M3 - Conference contribution

    SN - 9789048122585

    T3 - Advances in Experimental Medicine and Biology

    SP - 57

    EP - 63

    BT - Arterial Chemoreceptors

    A2 - Gonzalez, C.

    A2 - Nurse, C. A.

    A2 - Peers, C.

    PB - Springer

    CY - BERLIN

    ER -

    Dallas ML, Scragg JL, Wyatt CN, Ross F, Hardie DG, Evans AM et al. Modulation of O-2 Sensitive K+ Channels by AMP-activated Protein Kinase. In Gonzalez C, Nurse CA, Peers C, editors, Arterial Chemoreceptors. BERLIN: Springer . 2009. p. 57-63. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-90-481-2259-2_6