Effect of iodothyronines on electrophysiological properties of rat papillary muscle fibres.

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We studied the effect of in vivo administration of 3,3',5-triiodo-L-thyronine (L-T3) and other iodothyronines to thyroidectomized rats on the heart rate and electrophysiological properties, recorded in vitro, from papillary muscle fibres. The treatment with a daily substitutive L-T3 dose (3.7 nmoles/100 g body weight) for ten days was associated with a significant increase of heart rate and reduction of the action potential duration (APD) in comparison to that recorded from thyroidectomized rats. Analogous changes were obtained by treatment with equimolar dose of iodothyronines, such as 3,3',5-triiodo-D-thyronine (D-T3), 3,3',5,5'-L-tetraiodothyronine (L-T4), and 3'-isopropyl-3,5-diiodothyronine (3'-Ip-T2), but not by treatment with 3,3',5'-L-triiodothyronine (L-rT3). Unlike the heart rate, APD was found in close correlation with the relative occupancy by iodothyronines of the heart thyroid hormone-specific nuclear sites reported in literature. Such a pattern was little modified when the stimulation rate of the preparations was increased from 1 Hz to 5 Hz, nearing the physiological rates. In fact, there were no significant APD changes for all groups, and only the significance of the APD difference between the T + L-T3 and T + L-rT3 groups was modified. In accordance to the expectations, L-T4 showed appreciable effects on APD at both frequencies tested, despite its small affinity for nuclear receptors. Indeed, it is well-known that a substantial proportion of the T4 effect derives from peripheral conversion to T3. Therefore, our results support the hypothesis that the long-term effects of thyroid hormone on ventricular electrophysiological properties are induced via synthesis of proteins that are part of ionic channels, through a pathway involving hormone interaction with the cell nucleus.