Regulation of Rat Cardiac Kv1.5 Gene Expression by Thyroid Hormone Is Rapid and Chamber Specific1

• Published in: Endocrinology (Philadelphia) Vol. 140; no. 7; pp. 3170 - 3176
• Main Authors: Ojamaa, Kaie, Sabet, Amin, Kenessey, Agnes, Shenoy, Rajesh, Klein, Irwin
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01-07-1999
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.140.7.6776

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.