Regulation of rat cardiac Kv1.5 gene expression by thyroid hormone is rapid and chamber specific

Thyroid hormone affects the contractile and electrophysiological properties of the cardiac myocyte that result in part hom changes in the expression o f thyroid hormone-responsive cardiac genes, including those that regulate m embrane ion currents. To determine the molecular mechanisms underlying this effect, expression of a voltage-gated K+ channel, Kv1.5, was measured in r esponse to thyroid hormone. Using quantitative RT-PCR methodology, the cont ent of Kv1.5 messenger RNA (mRNA) in left ventricles of euthyroid rats was 4.25 +/- 0.6 x 10(-20) mol/mu g total RNA and was decreased by 70% in the h ypothyroid rat ventricle to 1.27 +/- 0.80 x 10(-20) mol/mu g RNA (P < 0.01) . Administration of T-3 to hypothyroid animals restored ventricular Kv1.5 m RNA to control levels within 1 h of treatment, making this the most rapid T -3-responsive cardiac gene reported to date. The half-life of Kv1.5 mRNA wa s 1.9 h and 2.0 h in euthyroid and hypothyroid ventricles, respectively, an d T-3 treatment of the rats did not alter its half-life. In atrial myocardi um, expression of Kv1.5 mRNA (6.10 +/- 0.37 x 10(-20) mol/mu g RNA) was una ltered by thyroid hormone status. The myocyte-specific and chamber-selectiv e expression of Kv1.5 mRNA was confirmed in primary cultures of rat atrial and ventricular myocytes.