K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK

N. Gamper, S. Fillon, Y. Feng, B. Friedrich, P. A. Lang, G. Henke, S. M. Huber, F. Lang, T. Kobayashi, P. Cohen

    Research output: Contribution to journalArticlepeer-review

    65 Citations (Scopus)

    Abstract

    The serum- and glucocorticoid-dependent kinase SGK1 was originally identified as a glucocorticoid-sensitive gene. Subsequently, the two homologous kinases SGK2 and SGK3 have been cloned, being products of distinct genes, which are differentially expressed and share 80% identity in amino acid sequence in their catalytic domains. While SGK1 has been shown to activate ion channels, including K+ channels, the functions of SGK2 and SGK3 have not been examined. The present study was therefore performed to elucidate the effect of SGK1, SGK2, and SGK3 on electrical properties of renal epithelial cells. To this end human embryonic kidney (HEK293) cells were transfected with the kinases and ion-channel activity determined using the patch-clamp technique. In non-transfected cells and in cells transfected with the empty GFP construct a voltage-gated K+ current was observed amounting to 303±19 pA (n=13) and 299±29 pA (n=23), respectively. Transfection with SGK1, SGK2 or SGK3 increased the voltage-gated K+ current to 1056±152 pA (n=17), 555±47 pA (n=17), and 775±98 pA (n=16), respectively. The K+ current was fully blocked by 3 mM tetraethylammonium chloride and inhibited 45% by the Kv1 channel blocker margatoxin (10 nM). In dual electrode voltage-clamp experiments SGK isoforms up-regulated Kv1 voltage-gated K+channels expressed in Xenopus laevis oocytes. The present observations thus reveal a powerful stimulating effect of all three isoforms of SGK on K+ channels. Those effects may participate in regulation of epithelial transport, cell proliferation, and neuromuscular excitability.

    Original languageEnglish
    Pages (from-to)60-66
    Number of pages7
    JournalPflugers Archiv European Journal of Physiology
    Volume445
    Issue number1
    DOIs
    Publication statusPublished - 1 Oct 2002

    Keywords

    • HEK293 cells
    • Kv1
    • Margatoxin
    • Patch-clamp
    • Potassium channels
    • SGK
    • TEA
    • Voltage clamp

    ASJC Scopus subject areas

    • Physiology
    • Clinical Biochemistry
    • Physiology (medical)

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