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

117 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 - 2002 Mar 11
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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