Regulation of Rat Cardiac Kv1.5 Gene Expression by Thyroid Hormone Is Rapid and Chamber Specific

• Published in: Endocrinology (Philadelphia) 1999-07, Vol.140 (7), p.3170-3176
• Main Authors: Ojamaa, Kaie, Sabet, Amin, Kenessey, Agnes, Shenoy, Rajesh, Klein, Irwin
• Format: Article
• Language: English
• Subjects: Cardiac muscle; Chambers; Channel gating; Gene expression; Gene regulation; Half-life; Heart; Hypothyroidism; Ion currents; Molecular modelling; Muscle contraction; Myocardium; Myocytes; Potassium channels (voltage-gated); Ribonucleic acid; RNA; Thyroid; Thyroid gland; Triiodothyronine; Ventricle
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.140.7.6776

Abstract Thyroid hormone affects the contractile and electrophysiological properties of the cardiac myocyte that result in part from changes in the expression of thyroid hormone-responsive cardiac genes, including those that regulate membrane ion currents. To determine the molecular mechanisms underlying this effect, expression of a voltage-gated K+ channel, Kv1.5, was measured in response to thyroid hormone. Using quantitative RT-PCR methodology, the content of Kv1.5 messenger RNA (mRNA) in left ventricles of euthyroid rats was 4.25± 0.6 × 10−20 mol/μg total RNA and was decreased by 70% in the hypothyroid rat ventricle to 1.27 ± 0.80 × 10−20 mol/μg RNA (P < 0.01). Administration of T3 to hypothyroid animals restored ventricular Kv1.5 mRNA to control levels within 1 h of treatment, making this the most rapid T3-responsive cardiac gene reported to date. The half-life of Kv1.5 mRNA was 1.9 h and 2.0 h in euthyroid and hypothyroid ventricles, respectively, and T3 treatment of the rats did not alter its half-life. In atrial myocardium, expression of Kv1.5 mRNA (6.10 ± 0.37 × 10−20 mol/μg RNA) was unaltered by thyroid hormone status. The myocyte-specific and chamber-selective expression of Kv1.5 mRNA was confirmed in primary cultures of rat atrial and ventricular myocytes.