Effects of Thyroid Hormone on the Calcium Current and Isoprenaline-induced Background Current in Rabbit Ventricular Myocytes

The majority of previous studies have been performed to explain the effects of thyroid hormone on the heart in chronic hyperthyroidism that was usually induced by eight to 10 daily injections of thyroid hormones. However, it is unclear whether or not the electrophysiological effects result from the chronic manifestations of hyperthyroidism and whether thyroid hormone acts directly or indirectly on cardiac myocytes to alter cardiac electrophysiological properties. In order to examine the acute term electrophysiological effects of thyroid hormone applied in vitro and the mechanisms responsible for some of these effects, we investigated the modulatory effects of thyroid hormone on the calcium current and isoprenaline-induced background current in L-triiodothyronine-treated ventricular myocytes of the rabbit. The major findings were as follows. Over 5 h (range, 5-24 h) after treatment of L-triiodothyronine (1 μM) in vitro, the calcium current was increased significantly. Isoprenaline (1 μM) and cyclic AMP (100 μM) caused an increase in the calcium current in both euthyroid and hyperthyroid myocytes. The hyperthyroid myocytes were more sensitive to the effect of β-adrenergic stimulation on the calcium current and isoprenaline-activated background current. In euthyroid myocytes, acetylcholine (1 μM) produced no or little changes in the amplitude of the calcium current. In hyperthyroid myocytes, acetylcholine markedly reduced the calcium current, however, acetylcholine was ineffective in the presence of sufficient intracellular cyclic AMP (100 μM). Our results suggest that thyroid hormone can affect the cardiac myocytes directly. Furthermore, our results demonstrate that thyroid hormone affects the calcium current and isoprenaline-activated background current. These electrophysiological changes may explain, at least in part, the occurrence of positive inotropy and cardiac arrhythmias that is associated with hyperthyroidism.