AIMS: The reduced heart rate and prolonged QT(end) duration in mice deficient in 
thyroid hormone receptor (TR) alpha1 may involve aberrant expression of the K(+) 
channel alpha-subunit KCNQ1 and its regulatory beta-subunit KCNE1. Here we focus 
on KCNE1 and study whether increased KCNE1 expression can explain changes in 
cardiac function observed in TRalpha1-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 TRalpha1. 
Overexpression of KCNE1 with a heart-specific promoter in transgenic mice 
resulted in a cardiac phenotype similar to that in TRalpha1-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 
TRalpha1-dependent repression of KCNE1 expression.