Mohammad Reza Toliat4, Peter Nürnberg4, Atakan Aydin1, Friedrich. C. Luft1 and ..... 23 Biondi RM, Kieloch A, Currie RA, Deak. M, Alessi DR: The ... glucocorticoid-induced protein kinase. (Sgk) by cyclic AMP and insulin. J Biol. Chem 2001 ...
Original Paper
Cellular Physiology and Biochemistr Biochemistryy
Cell Physiol Biochem 2004;14:135-142
Accepted: Oktober 24, 2003
Association of the Serum and Glucocorticoid Regulated Kinase (sgk1) Gene with QT Interval Andreas Busjahn 1,2 , Guiscard Seebohm 3 , Gottlieb Maier 3 , Mohammad Reza Toliat4, Peter Nürnberg4, Atakan Aydin1, Friedrich C. Luft1 and Florian Lang3 Franz Volhard Clinic, HELIOS Kliniken-Berlin and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, 2HealthTwiSt GmbH, Berlin, 3Department of Physiology, University of Tübingen, 4Gene Mapping Center (GMC), Max-Delbrück-Centrum, Berlin 1
Key Words Long QT syndrome • ECG • Cardiac action potential • KCNE1 • KCNQ1 • QT intervall • Nucleotide polymorphism Abstract The serum and glucocorticoid inducible kinase (SGK1) is well known to up-regulate the renal epithelial Na+ channel ENaC. Excessive SGK1 activity would be expected to cause renal Na+ retention and blood pressure increase. Certain polymorphisms of the SGK1 gene (E8CC/CT;I6CC) are indeed associated with moderately enhanced blood pressure. We have recently disclosed another function of SGK1, i.e. the stimulation of the slowly activating K+ channel KCNE1/ KCNQ1. Among the functions of this channel is the repolarisation of cardiac myocytes. Accordingly, defective KCNE1 and/or KCNQ1 lead to long QT syndrome, a disorder causing fainting and sudden cardiac death. In the present study we demonstrate that coexpression of SGK1 in Xenopus oocytes increases KCNQ1/KCNE1 induced current without significantly altering voltage dependence, activation and deactivation kinetics. To test for the relevance of SGK1 in human cardiac repolarization, we analysed the ECG of monozygotic (MZ) (126 pairs) and
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dizygotic (DZ) (70 pairs) twin subjects and parents of DZ twins. The E8CC/CT;I6CC polymorphism was indeed significantly (p
