Evidence that decreased heart rate in thyroid hormone receptor-alpha1-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-alpha1 (TRalpha1). We have previously reported that the TRalpha1-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 (T3) was given once a day, there was a parallel increase in heart rate (occurring 1 day later in the TRalpha1-deficient mice than in controls) and body temperature. Analysis of single-lead ECG revealed a prolonged QRS and Q-Tend time in the TRalpha1-deficient mice, which was shortened after T3 treatment. Monophasic action potential durations, measured in hearts from anesthetized mice at 90% of repolarization, were significantly prolonged in TRalpha1-deficient mice. Air-jet stress and a single injection of an anticholinergic agent induced a parallel increase, and a beta-adrenergic receptor blocker induced a decrease in heart rate in both groups. There was no difference in beta-adrenergic receptor density. The results indicate that the TRalpha1-deficient mice have a specific defect in intrinsic heart rate regulation.
Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden.
C
C
Johansson
B
B
Vennström
P
P
Thorén
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000172:deficiency* / Q000502:physiology; D014284:Triiodothyronine / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine