Electrophysiological effects of thyroid hormones in guinea-pig ventricular muscle: Time course and relationships to blood levels

Chronic alterations in the thyroid state have been shown to induce marked changes in action potential characteristics, the most pronounced being shortening of action potential duration (APD) by hyperthyroidism and an increase in duration by hypothyroidism. In the present study our major objectives were to investigate the time course of the effect of thyroid hormone on action potential characteristics, to examine the relationships between thyroid hormone levels and these changes, and to test whether the electrophysiological alterations are induced both by thyroxine (T₄) and triiodothyronine (T₃). The major findings were that a single dose of either hormone (100 μg/kg) caused a marked shortening of APD, while resting potential, action potential amplitude and V ̇_max were unchanged. APD shortening was observed promptly after ip T₄ or T₃ administration, with maximal effect occurring within 2 to 3 hrs. Having determined thyroid hormone levels in the guinea-pigs used for the electrophysiological experiments, we found a close temporal association and inverse linear relationships (r = -0.82) between total T₄ levels and APD. To determine whether APD shortening is induced due to a direct effect of thyroid hormone on the myocardium, euthyroid papillary muscles were superfused with 10^-6mT₃; within 3 hrs of superfusion with T₃, APD was shortened from 148.8 ± 4.7 ms to 117.7 ± 6.4 ms (P < 0.01), an effect blocked by the protein synthesis inhibitor cycloheximide. Our results demonstrate that thyroid hormones affect the duration of the ventricular action potential in a concentration dependent fashion. Furthermore, the study suggests that thyroid hormones affect the myocardium directly via mechanism(s) that are probably associated with thyroid hormone-related protein synthesis.