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Table of Contents
Vol. 19, No. 1-4, 2007
Issue release date: January 2007
Section title: Original Paper
Cell Physiol Biochem 2007;19:021–032
(DOI:10.1159/000099189)

KCNE Beta Subunits Determine pH Sensitivity of KCNQ1 Potassium Channels

Heitzmann D.* · Koren V.* · Wagner M.# · Sterner C.# · Reichold M.# · Tegtmeier I.# · Volk T.# · Warth R.#
Institute of Physiology, University of Regensburg,#Institute of Cellular and Molecular Physiology, University of Erlangen-Nürnberg,*These authors contributed equally
email Corresponding Author

Prof. Dr. Richard Warth

Institute of Physiology

Universitaetstrasse 31, 93053 Regensburg (Germany)

Tel. +49-941-943-2894, Fax: +49-941-943-2896

E-Mail richard.warth@vkl.uni-regensburg.de

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Abstract

Background/Aims: Heteromeric KCNEx/KCNQ1 (=KvLQT1, Kv7.1) K+ channels are important for repolarization of cardiac myocytes, endolymph secretion in the inner ear, gastric acid secretion, and transport across epithelia. They are modulated by pH in a complex way: homomeric KCNQ1 is inhibited by external acidification (low pHe); KCNE2/KCNQ1 is activated; and for KCNE1/KCNQ1, variable effects have been reported. Methods: The role of KCNE subunits for the effect of pHe on KCNQ1 was analyzed in transfected COS cells and cardiac myocytes by the patch-clamp technique. Results: In outside-out patches of transfected cells, hKCNE2/hKCNQ1 current was increased by acidification down to pH 4.5. Chimeras with the acid-insensitive hKCNE3 revealed that the extracellular N-terminus and at least part of the transmembrane domain of hKCNE2 are needed for activation by low pHe. hKCNE1/hKCNQ1 heteromeric channels exhibited marked changes of biophysical properties at low pHe: The slowly activating hKCNE1/hKCNQ1 channels were converted into constitutively open, non-deactivating channels. Experiments on guinea pig and mouse cardiac myocytes pointed to an important role of KCNQ1 during acidosis implicating a significant contribution to cardiac repolarization under acidic conditions. Conclusion: External pH can modify current amplitude and biophysical properties of KCNQ1. KCNE subunits work as molecular switches by modulating the pH sensitivity of human KCNQ1.

© 2007 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: January 16, 2007
Issue release date: January 2007

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


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