Thyroid hormone has profound direct effects on cardiac function, but the 
hormonal interactions with the autonomic control of heart rate are unclear. 
Because thyroid hormone receptor (TR)-alpha1 has been implicated in the 
autonomic control of brown adipose energy metabolism, it might also play an 
important role in the central autonomic control of heart rate. Thus, we aimed to 
analyze the role of TRalpha1 signaling in the autonomic control of heart rate 
using an implantable radio telemetry system. We identified that mice expressing 
the mutant TRalpha1R384C (TRalpha1+m mice) displayed a mild bradycardia, which 
becomes more pronounced during night activity or on stress and is accompanied by 
a reduced expression of nucleotide-gated potassium channel 2 mRNA in the heart. 
Pharmacological blockage with scopolamine and the beta-adrenergic receptor 
antagonist timolol revealed that the autonomic control of cardiac activity was 
similar to that in wild-type mice at room temperature. However, at 
thermoneutrality, in which the regulation of heart rate switches from 
sympathetic to parasympathetic in wild-type mice, TRalpha1+m mice maintained 
sympathetic stimulation and failed to activate parasympathetic signaling. Our 
findings demonstrate a novel role for TRalpha1 in the adaptation of cardiac 
activity by the autonomic nervous system and suggest that human patients with a 
similar mutation in TRalpha1 might exhibit a deficit in cardiac adaptation to 
stress or physical activity and an increased sensitivity to beta-blockers.