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Thyroid hormone receptor α can control action potential duration in mouse ventricular myocytes through the KCNE1 ion channel subunit
Author(s) -
Mansén A.,
Tiselius C.,
Sand P.,
Fauconnier J.,
Westerblad H.,
Rydqvist B.,
Vennström B.
Publication year - 2010
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2009.02052.x
Subject(s) - endocrinology , medicine , chinese hamster ovary cell , western blot , biology , receptor , myocyte , chemistry , gene , biochemistry
Abstract Aims: The reduced heart rate and prolonged QT end duration in mice deficient in thyroid hormone receptor (TR) α1 may involve aberrant expression of the K + channel α‐subunit KCNQ1 and its regulatory β‐subunit KCNE1. Here we focus on KCNE1 and study whether increased KCNE1 expression can explain changes in cardiac function observed in TRα1‐deficient mice. Methods: TR‐deficient, KCNE1‐overexpressing and their respective wildtype (wt) mice were used. mRNA and protein expression were assessed with Northern and Western blot respectively. Telemetry was used to record electrocardiogram and temperature in freely moving mice. Patch‐clamp was used to measure action potentials (APs) in isolated cardiomyocytes and ion currents in Chinese hamster ovary (CHO) cells. Results: KCNE1 was four to 10‐fold overexpressed in mice deficient in TRα1. Overexpression of KCNE1 with a heart‐specific promoter in transgenic mice resulted in a cardiac phenotype similar to that in TRα1‐deficient mice, including a lower heart rate and prolonged QT end time. Cardiomyocytes from KCNE1‐overexpressing mice displayed increased AP duration. CHO cells transfected with expression plasmids for KCNQ1 and KCNE1 showed an outward rectifying current that was maximal at equimolar plasmids for KCNQ1‐KCNE1 and decreased at higher KCNE1 levels. Conclusion: The bradycardia and prolonged QT end time in hypothyroid states can be explained by altered K + channel function due to decreased TRα1‐dependent repression of KCNE1 expression.