© 1999 American Heart Association, Inc.
Molecular Medicine |
Thyroid Hormone Regulates Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel (HCN2) mRNA in the Rat Heart
From the Thyroid Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (J.P., P.R.L.), Boston, Mass; the Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine (L.A.B.), Pa; and Department of Internal Medicine and Endocrinology, The Medical University of Warsaw (J.P.), Poland.
Correspondence to Janusz Pachucki, MD, Department of Internal Medicine and Endocrinology, The Medical University of Warsaw, ul. Banacha 1 a, 02-097 Warsaw, Poland. E-mail janusz.pachucki{at}amwaw.edu.pl
Abstract—Thyroid hormone regulation of the cardiac pacemaker gene, the hyperpolarization-activated cyclic nucleotide-gated channel gene (HCN2), was studied in rats by Northern analysis. Thyroid hormone administration to hypothyroid rats resulted in a doubling of the HCN2/ß-actin mRNA ratio. A smaller, not statistically significant, increase in HCN2 mRNA occurred when euthyroid animals were made hyperthyroid. A single large dose of L-triiodothyronine given to hypothyroid rats caused a 4.7-fold increase in myocardial HCN2 mRNA expression level and only a 2.3-fold increase in the ß-actin mRNA level. Although the rat HCN2 promoter has not been cloned, we identified a consensus thyroid hormone response element in the promoter sequence of the human HCN2 gene. Therefore, the increase in rat HCN2 mRNA is likely due to L-triiodothyronine stimulation of HCN2 gene transcription. The results suggest that the regulation of heart rate by thyroid hormone may be explained, at least in part, by the positive effect of this hormone on HCN2 gene expression.
Key Words: HCN2 • heart • triiodothyronine • transcription
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