title: Regulation of rat cardiac Kv1.5 gene expression by thyroid hormone is rapid and chamber specific.
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+/-0.6x10(-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.
authors.affiliation: Department of Medicine, North Shore University Hospital/New York University School of Medicine, Manhasset 11030, USA. kojamaa@nshs.edu
authors.forename: K
authors.initials: K
authors.lastname: Ojamaa
authors.forename: A
authors.initials: A
authors.lastname: Sabet
authors.forename: A
authors.initials: A
authors.lastname: Kenessey
authors.forename: R
authors.initials: R
authors.lastname: Shenoy
authors.forename: I
authors.initials: I
authors.lastname: Klein
mesh_terms: 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*
chemical_list: C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D014284:Triiodothyronine