Effects of thyroid and glucocorticoid hormones on Kv1.5 potassium channel gene expression in the rat left ventricle.

The effects of thyroid and glucocorticoid hormones on the expression of the Kv1.5 potassium channel gene were studied in the rat left ventricle. Rats were rendered hypothyroid by oral administration of methimazole (MMI). Hyperthyroidism was induced in the MMI-treated rats by administration of L-thyroxine (T4). Kv1.5 mRNA levels decreased markedly in the hypothyroid rats, whereas they increased in the hyperthyroid rats. Propranolol, a beta-adrenergic blocker, did not inhibit the T4-dependent increase in Kv1.5 mRNA, indicating that the increase is not due to the increased beta-adrenergic stimuli under hyperthyroidism. Accordingly, treatment of the MMI-treated hypothyroid rats with isoproterenol, a beta-adrenergic receptor agonist, did not increase the mRNA. The Kv1.5 mRNA levels positively correlated with the thyroid hormone levels in sera. When rats were adrenalectomized and rendered hypothyroid, Kv1.5 mRNA become undetectable. Administration of 3,3',5-triiodothyronine (T3) at a dose to induce hyperthyroidism did not restore the mRNA level. However, T3 significantly increased the mRNA level when dexamethasone was co-administered at a physiological dose. These results for the first time demonstrate that thyroid hormone up-regulates Kv1.5 mRNA levels in the rat left ventricle and they demonstrate that glucocorticoid is required for this induction.