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Regulation of KCNE1-dependent K+ current by the serum and glucocorticoid-inducible kinase (SGK) isoforms

  • Ion Channels, Transporters
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Abstract

The slowly activating K+ channel subunit KCNE1 is expressed in a variety of tissues including proximal renal tubules, cardiac myocytes and stria vascularis of inner ear. The present study has been performed to explore whether the serum- and glucocorticoid-inducible kinase family members SGK1, SGK2, or SGK3 and/or protein kinase B (PKB) influence K+ channel activity in Xenopus oocytes expressing KCNE1. cRNA encoding KCNE1 was injected with or without cRNA encoding wild-type SGK1, constitutively active S422DSGK1, inactive K127 NSGK1, wild-type SGK2, wild-type SGK3 or constitutively active T308D,S473DPKB. In oocytes injected with KCNE1 cRNA but not in water-injected oocytes a depolarization from −80 mV to −10 mV led to the appearance of a slowly activating K+ current. Coexpression of SGK1, S422DSGK1, SGK2, SGK3 or T308D,S473DPKB but not K127 NSGK1 significantly stimulated KCNE1-induced current. The effect did not depend on Na+/K+-ATPase activity. KCNE1-induced current was markedly upregulated by coexpression of KCNQ1 and further increased by additional expression of S422DSGK1, SGK2, SGK3 or T308D,S473DPKB. In conclusion, all three members of the SGK family of kinases SGK1–3 and protein kinase B stimulate the slowly activating K+ channel KCNE1/KCNQ1. The kinases may thus participate in the regulation of KCNE1-dependent transport and excitability.

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Acknowledgements

The authors thank Sir Philip Cohen for valuable discussion and providing the constructs of SGK2 SGK3 and PKB. This study was supported by the Deutsche Forschungsgemeinschaft La 315/4-1, Va 118/7-1, the Mukoviszidose e.V., by a grant from the Federal Ministry of Education, Science, Research and Technology (Fö 01KS9602) and the Interdisciplinary Center for Clinical Research.

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, 72076 , Tübingen, Germany

    Hamdy M. Embark, Christoph Böhmer & Florian Lang

  2. Department of Pharmacology, University of Tübingen, 72074, Tübingen, Germany

    Volker Vallon

  3. Department of Internal Medicine, Charite, 13125, Berlin, Germany

    Friedrich Luft

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  1. Hamdy M. Embark
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  2. Christoph Böhmer
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Correspondence to Florian Lang.

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Embark, H.M., Böhmer, C., Vallon, V. et al. Regulation of KCNE1-dependent K+ current by the serum and glucocorticoid-inducible kinase (SGK) isoforms. Pflugers Arch - Eur J Physiol 445, 601–606 (2003). https://doi.org/10.1007/s00424-002-0982-y

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