Evidence that decreased heart rate in thyroid hormone receptor-α1-deficient mice is an intrinsic defect

Using a telemetry system with implantable transmitters, we recorded heart rate, electrocardiogram (ECG), body temperature, and locomotor activity continuously in awake, freely moving mice deficient in the thyroid hormone receptor-α1 (TR ). We have previously reported that the TR -deficient mice have a 20% lower mean heart rate and a 0.5°C lower body temperature compared with wild-type control animals. In this study we found that when 3,5,3'-triiodothyronine (T ) was given once a day, there was a parallel increase in heart rate (occurring 1 day later in the TR -deficient mice than in controls) and body temperature. Analysis of single-lead ECG revealed a prolonged QRS and Q-T time in the TR -deficient mice, which was shortened after T treatment. Monophasic action potential durations, measured in hearts from anesthetized mice at 90% of repolarization, were significantly prolonged in TR -deficient mice. Air-jet stress and a single injection of an anticholinergic agent induced a parallel increase, and a β-adrenergic receptor blocker induced a decrease in heart rate in both groups. There was no difference in β-adrenergic receptor density. The results indicate that the TR -deficient mice have a specific defect in intrinsic heart rate regulation.