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

doi:10.1007/s00424-001-0741-5

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 journal › Article › peer-review

122 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 language	English
Pages (from-to)	625-634
Number of pages	10
Journal	Pflugers Archiv European Journal of Physiology
Volume	443
Issue number	4
DOIs	https://doi.org/10.1007/s00424-001-0741-5
Publication status	Published - 11 Mar 2002

Keywords

Cell proliferation
Growth factor
Kv1.3
Margatoxin
Wortmannin

ASJC Scopus subject areas

Physiology
Clinical Biochemistry
Physiology (medical)

Access to Document

10.1007/s00424-001-0741-5Licence: No Licence / Unknown

Cite this

@article{e0a3ee7ae7a64c59a212deccafabe118,

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

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.",

keywords = "Cell proliferation, Growth factor, Kv1.3, Margatoxin, Wortmannin",

author = "N. Gamper and S. Fillon and S. Huber and Y. Feng and T. Kobayashi and P. Cohen and F. Lang",

year = "2002",

month = mar,

day = "11",

doi = "10.1007/s00424-001-0741-5",

language = "English",

volume = "443",

pages = "625--634",

journal = "Pflugers Archiv European Journal of Physiology",

issn = "0031-6768",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "4",

}

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

UR - https://www.scopus.com/pages/publications/0036191636

U2 - 10.1007/s00424-001-0741-5

DO - 10.1007/s00424-001-0741-5

M3 - Article

C2 - 11907830

AN - SCOPUS:0036191636

SN - 0031-6768

VL - 443

SP - 625

EP - 634

JO - Pflugers Archiv European Journal of Physiology

JF - Pflugers Archiv European Journal of Physiology

IS - 4

ER -