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Regulation of cardiac shal-related potassium channel Kv 4.3 by serum- and glucocorticoid-inducible kinase isoforms in Xenopus oocytes

  • Cardiovascular System
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Abstract

The human cardiac transient outward potassium current Ito is formed by co-assembly of voltage-dependent K+ channel (Kv 4.3) pore-forming α-subunits with differently spliced K channel interacting protein (KChIP) accessory proteins. Ito is of considerable importance for the normal course of the cardiac ventricular action potential. The present study was performed to determine whether isoforms of the serum- and glucocorticoid-inducible kinase (SGK) family influence Kv 4.3/KChIP2b channel activity in the Xenopus laevis heterologous expression system. Co-expression of SGK1, but not of SGK2 or SGK3, increased Kv 4.3/KChIP2b channel currents. The up-regulation of the current was not due to changes in the activation curve or changes of channel inactivation. The currents in oocytes expressing Kv 4.3 alone were smaller than those in Kv 4.3/KChIP2b expressing oocytes, but were still stimulated by SGK1. The effect of wild-type SGK1 was mimicked by constitutively active SGK1 (SGK1 S422D) but not by an inactive mutant (SGK1 K127N). The current amplitude increase mediated by SGK1 was not dependent on NEDD4.2 or RAB5, nor did it reflect increased cell surface expression. In conclusion, SGK1 stimulates Kv 4.3 potassium channels expressed in Xenopus oocytes by a novel mechanism distinct from the known NEDD4.2-dependent pathway.

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Acknowledgements

The clones Kv4.3 and KChIP2b were a kind gift from Aventis Pharma Deutschland GmbH, the clone Kv4.3(HA) was a kind gift from N. Decher and M.C. Sanguinetti and RAB5 was a kind gift from C. Bucci. We thank Dr. Klaus Steinmeyer for helpful discussion and comments on the manuscript.

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

    Ravshan Baltaev, Nathalie Strutz-Seebohm, Ganna Korniychuk, Svetlana Myssina, Florian Lang & Guiscard Seebohm

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  1. Ravshan Baltaev
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  2. Nathalie Strutz-Seebohm
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  3. Ganna Korniychuk
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Correspondence to Guiscard Seebohm.

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Baltaev, R., Strutz-Seebohm, N., Korniychuk, G. et al. Regulation of cardiac shal-related potassium channel Kv 4.3 by serum- and glucocorticoid-inducible kinase isoforms in Xenopus oocytes. Pflugers Arch - Eur J Physiol 450, 26–33 (2005). https://doi.org/10.1007/s00424-004-1369-z

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