EVIDENCE THAT DECREASED HEART-RATE IN THYROID-HORMONE RECEPTOR-ALPHA-1-DEFICIENT MICE IS AN INTRINSIC DEFECT

Using a telemetry system with implantable transmitters, we recorded he art rate, electrocardiogram (ECG), body temperature, and locomotor act ivity continuously in awake, freely moving mice deficient in the thyro id hormone receptor-alpha 1 (TRalpha 1). We have previously reported t hat the TRalpha 1-deficient mice have a 20% lower mean heart rate and a 0.5 degrees C lower body temperature compared with wild-type control animals. In this study we found that when 3,5,3'-triiodothyronine (T- 3) was given once a day, there was a parallel increase in heart rate ( occurring 1 day later in the TRalpha 1-deficient mice than in controls ) and body temperature. Analysis of single-lead ECG revealed a prolong ed QRS and Q-Tend time in the TRalpha 1-deficient mice, which was shor tened after T-3 treatment. Monophasic action potential durations, meas ured in hearts from anesthetized mice at 90% of repolarization, were s ignificantly prolonged in TRalpha 1-deficient mice. Air-jet stress and a single injection of an anticholinergic agent induced a parallel inc rease, and a beta-adrenergic receptor blocker induced a decrease in he art rate in both groups. There was no difference in beta-adrenergic re ceptor density. The results indicate that the TRalpha 1-deficient mice have a specific defect in intrinsic heart rate regulation.