IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1

N. Gamper, S. Fillon, S. Huber, Y. Feng, T. Kobayashi, P. Cohen, F. Lang

    Research output: Contribution to journalArticle

    116 Citations (Scopus)

    Abstract

    Involvement of voltage-gated (Kv) potassium channels in IGF-1-induced proliferation of HEK293 cells was studied by patch-clamp, RT-PCR and FACS analysis. IGF-1 up-regulated outwardly rectifying whole-cell K+ current starting after 1 h of incubation and reaching a maximum after 4-6 h. The IGF-1-stimulated current was voltage-gated with an activation threshold of -30 mV to -40 mV, a half-maximal activation at +5.3±1.8 mV, and time constants for activation and inactivation of 4.5±0.4 ms and 43.5±5.6 ms (n=10), respectively. The current was inhibited by TEA, margatoxin, agitoxin-2 and stichodactyla toxin. PCR amplification of different Kv subunits from HEK293 cDNA demonstrated the expression of Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv3.1 and Kv3.4 mRNA. Quantitative RT-PCR showed up-regulation of Kv1.1, 1.2 and 1.3 mRNA by IGF-1. The effect of IGF-1 on K+ current was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), wortmannin and LY294002, and mimicked by overexpression of human 3-phosphoinositide-dependent protein kinase-1 (hPDK1) or serum- and glucocorticoid-dependent kinase-1 (hSGK1), both sequential downstream targets of PI3-kinase. IGF-1-induced proliferation of HEK293 cells was inhibited by both K+ channel blockers and inhibitors of PI3-kinase. In conclusion, IGF-1 through PI3-kinase, PDK1 and SGK1 up-regulates Kv channels, an effect required for the proliferative action of the growth factor.

    Original languageEnglish
    Pages (from-to)625-634
    Number of pages10
    JournalPflugers Archiv European Journal of Physiology
    Volume443
    Issue number4
    DOIs
    Publication statusPublished - 11 Mar 2002

    Fingerprint

    Phosphatidylinositol 3-Kinase
    Insulin-Like Growth Factor I
    Up-Regulation
    Voltage-Gated Potassium Channels
    HEK293 Cells
    Chemical activation
    Polymerase Chain Reaction
    Messenger RNA
    2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
    Clamping devices
    Electric potential
    Glucocorticoids
    Amplification
    Intercellular Signaling Peptides and Proteins
    Phosphotransferases
    Complementary DNA
    Serum

    Keywords

    • Cell proliferation
    • Growth factor
    • Kv1.3
    • Margatoxin
    • Wortmannin

    Cite this

    Gamper, N. ; Fillon, S. ; Huber, S. ; Feng, Y. ; Kobayashi, T. ; Cohen, P. ; Lang, F. / IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1. In: Pflugers Archiv European Journal of Physiology. 2002 ; Vol. 443, No. 4. pp. 625-634.
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    abstract = "Involvement of voltage-gated (Kv) potassium channels in IGF-1-induced proliferation of HEK293 cells was studied by patch-clamp, RT-PCR and FACS analysis. IGF-1 up-regulated outwardly rectifying whole-cell K+ current starting after 1 h of incubation and reaching a maximum after 4-6 h. The IGF-1-stimulated current was voltage-gated with an activation threshold of -30 mV to -40 mV, a half-maximal activation at +5.3±1.8 mV, and time constants for activation and inactivation of 4.5±0.4 ms and 43.5±5.6 ms (n=10), respectively. The current was inhibited by TEA, margatoxin, agitoxin-2 and stichodactyla toxin. PCR amplification of different Kv subunits from HEK293 cDNA demonstrated the expression of Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv3.1 and Kv3.4 mRNA. Quantitative RT-PCR showed up-regulation of Kv1.1, 1.2 and 1.3 mRNA by IGF-1. The effect of IGF-1 on K+ current was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), wortmannin and LY294002, and mimicked by overexpression of human 3-phosphoinositide-dependent protein kinase-1 (hPDK1) or serum- and glucocorticoid-dependent kinase-1 (hSGK1), both sequential downstream targets of PI3-kinase. IGF-1-induced proliferation of HEK293 cells was inhibited by both K+ channel blockers and inhibitors of PI3-kinase. In conclusion, IGF-1 through PI3-kinase, PDK1 and SGK1 up-regulates Kv channels, an effect required for the proliferative action of the growth factor.",
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    Gamper, N, Fillon, S, Huber, S, Feng, Y, Kobayashi, T, Cohen, P & Lang, F 2002, 'IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1', Pflugers Archiv European Journal of Physiology, vol. 443, no. 4, pp. 625-634. https://doi.org/10.1007/s00424-001-0741-5

    IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1. / Gamper, N.; Fillon, S.; Huber, S.; Feng, Y.; Kobayashi, T.; Cohen, P.; Lang, F.

    In: Pflugers Archiv European Journal of Physiology, Vol. 443, No. 4, 11.03.2002, p. 625-634.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1

    AU - Gamper, N.

    AU - Fillon, S.

    AU - Huber, S.

    AU - Feng, Y.

    AU - Kobayashi, T.

    AU - Cohen, P.

    AU - Lang, F.

    PY - 2002/3/11

    Y1 - 2002/3/11

    N2 - Involvement of voltage-gated (Kv) potassium channels in IGF-1-induced proliferation of HEK293 cells was studied by patch-clamp, RT-PCR and FACS analysis. IGF-1 up-regulated outwardly rectifying whole-cell K+ current starting after 1 h of incubation and reaching a maximum after 4-6 h. The IGF-1-stimulated current was voltage-gated with an activation threshold of -30 mV to -40 mV, a half-maximal activation at +5.3±1.8 mV, and time constants for activation and inactivation of 4.5±0.4 ms and 43.5±5.6 ms (n=10), respectively. The current was inhibited by TEA, margatoxin, agitoxin-2 and stichodactyla toxin. PCR amplification of different Kv subunits from HEK293 cDNA demonstrated the expression of Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv3.1 and Kv3.4 mRNA. Quantitative RT-PCR showed up-regulation of Kv1.1, 1.2 and 1.3 mRNA by IGF-1. The effect of IGF-1 on K+ current was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), wortmannin and LY294002, and mimicked by overexpression of human 3-phosphoinositide-dependent protein kinase-1 (hPDK1) or serum- and glucocorticoid-dependent kinase-1 (hSGK1), both sequential downstream targets of PI3-kinase. IGF-1-induced proliferation of HEK293 cells was inhibited by both K+ channel blockers and inhibitors of PI3-kinase. In conclusion, IGF-1 through PI3-kinase, PDK1 and SGK1 up-regulates Kv channels, an effect required for the proliferative action of the growth factor.

    AB - Involvement of voltage-gated (Kv) potassium channels in IGF-1-induced proliferation of HEK293 cells was studied by patch-clamp, RT-PCR and FACS analysis. IGF-1 up-regulated outwardly rectifying whole-cell K+ current starting after 1 h of incubation and reaching a maximum after 4-6 h. The IGF-1-stimulated current was voltage-gated with an activation threshold of -30 mV to -40 mV, a half-maximal activation at +5.3±1.8 mV, and time constants for activation and inactivation of 4.5±0.4 ms and 43.5±5.6 ms (n=10), respectively. The current was inhibited by TEA, margatoxin, agitoxin-2 and stichodactyla toxin. PCR amplification of different Kv subunits from HEK293 cDNA demonstrated the expression of Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv3.1 and Kv3.4 mRNA. Quantitative RT-PCR showed up-regulation of Kv1.1, 1.2 and 1.3 mRNA by IGF-1. The effect of IGF-1 on K+ current was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), wortmannin and LY294002, and mimicked by overexpression of human 3-phosphoinositide-dependent protein kinase-1 (hPDK1) or serum- and glucocorticoid-dependent kinase-1 (hSGK1), both sequential downstream targets of PI3-kinase. IGF-1-induced proliferation of HEK293 cells was inhibited by both K+ channel blockers and inhibitors of PI3-kinase. In conclusion, IGF-1 through PI3-kinase, PDK1 and SGK1 up-regulates Kv channels, an effect required for the proliferative action of the growth factor.

    KW - Cell proliferation

    KW - Growth factor

    KW - Kv1.3

    KW - Margatoxin

    KW - Wortmannin

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