Different gene expression of potassium channels by thyroid hormone and an antithyroid drug between the atrium and ventricle of rats.

Abstract

Thyroid hormone has been shown to modulate the gene expression of cardiac potassium channels, however, it is not known if gene expression is different between the atrium and the ventricle. The long-term effects of thyroid hormone on nuclear thyroid hormone receptors are also not known. Triiodothyronine (T3) at 25 microg/100 g of body weight or propylthiouracil (PTU) at 4 mg/100 g of body weight was given to adult rats via a gastric tube for 14 days. The levels of mRNA of Kv1.2. Kv1.4, Kv1.5, Kv2.1, Kv4.2, erg, LQT1, and minK were assayed by RNase protection assay. The mRNA of nuclear T3-receptor-al and T3-receptor-beta1 were also assayed for 15 days. After T3 (or PTU), plasma free T3 and free T4 increased (or decreased) significantly. The mRNA levels of Kv1.2 and Kv1.4 were reduced after T3 in the atrium and the ventricle. while PTU increased the levels in both chambers. Kv1.5 was significantly up-regulated by T3 in the atrium and the ventricle (P < 0.02 for both) and PTU decreased its expression in the ventricle (P < 0.02). Kv2.1 and Kv4.2 were not affected by T3 or PTU. mRNA of erg was not affected by T3 in the atrium but decreased in the ventricle (P < 0.01). After PTU, erg mRNA was decreased in the atrium (P < 0.02) but increased in the ventricle (P < 0.01). LQT1 was decreased by T3 in both chambers (P < 0.01) and not affected by PTU. minK was not detectable in the control state and was up-regulated only in the atrium: a peak on the 4th day followed by a decline to the undetectable level on the 10-15th days. During T3 treatment, nuclear T3-receptor-alpha1 and beta1 mRNA were decreased in the initial 3 days but returned to control levels thereafter. Between the atrium and ventricle of the adult rat heart, the responses of gene expression of voltage-gated potassium channels to T3 or PTU were quantitatively or qualitatively different and the differential responses may explain cardiac manifestations of hyperthyroidism, which is a frequent complication of supraventricular arrhythmia.