Thyroid hormone regulates expression of shaker-related potassium channel mRNA in rat heart.
Effects of thyroid hormones on cardiac function or rhythm have been known; however, the mechanism is still unclear. In the present study examined were effects of triiodethyronine (T3) on voltage-gated potassium channel gene expression in rat heart since the potassium channels were presumed to modulate cardiac functions. The mRNA expression of five voltage-gated potassium channel gene alpha subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) in heart was examined by ribonuclease protection assay in rats which were treated with T3 or propylthyouracil (PTU). All these genes except Kv1.4 mRNA were apparently expressed in the normal rat heart ventricle. Kv1.2 mRNA expression in ventricle was markedly suppressed by T3-treatment and enhanced by PTU-treatment. Interestingly, upregulation of Kv1.4 mRNA expression and downregulation of Kv1.5 mRNA expression were concomitantly induced in the ventricle by the PTU-treatment. In addition, the downregulation of the ventricular Kv1.5 mRNA expression induced by PTU was restored by T3 replacement. No changes of Kv2.1 and Kv4.2 mRNA expression were observed in the ventricles by the T3- or PTU-treatment. In heart atrium the same findings were observed. Kv1.4 mRNA expression, which was detectable in control rat atrium, also decreased significantly by T3-treatment. In contrast, no changes of Kv1.2, Kv1.4, and Kv1.5 mRNA expression in rat brains were induced by T3-treatment. These findings suggest that thyroid hormone specifically influences mRNA expression of Shaker-related potassium channel genes in rat hearts through a common T3 receptor-mediated regulation at a transcriptional level.
Abe
A
A
First Department of Internal Medicine, Institute of Nephrology, Niigata University School of Medicine, Niigata, Japan.
Yamamoto
T
T
Isome
M
M
Ma
M
M
Yaoita
E
E
Kawasaki
K
K
Kihara
I
I
Aizawa
Y
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D015221:Potassium Channels / Q000235:genetics*; D011441:Propylthiouracil / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051637:Shaker Superfamily of Potassium Channels; D013963:Thyroid Hormones / Q000097:blood / Q000494:pharmacology*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology
D015221:Potassium Channels; D012333:RNA, Messenger; D051637:Shaker Superfamily of Potassium Channels; D013963:Thyroid Hormones; D014284:Triiodothyronine; D011441:Propylthiouracil; D013974:Thyroxine