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 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+/-0.6x10(-20) mol/microg total RNA and was decreased by 70% in the hypothyroid rat ventricle to 1.27+/-0.80x10(-20) mol/microg 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+/-0.37x10(-20) mol/microg 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.
Ojamaa
K
K
Department of Medicine, North Shore University Hospital/New York University School of Medicine, Manhasset 11030, USA. kojamaa@nshs.edu
Sabet
A
A
Kenessey
A
A
Shenoy
R
R
Klein
I
I
D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D006207:Half-Life; D006321:Heart / Q000502:physiology*; D006980:Hyperthyroidism / Q000378:metabolism / Q000473:pathology; D007037:Hypothyroidism / Q000378:metabolism / Q000473:pathology; D051666:Kv1.5 Potassium Channel; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*
C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D014284:Triiodothyronine