Different Gene Expression of Potassium Channels by Thyroid Hormone and an Antithyroid Drug Between the Atrium and Ventricle of Rats
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概要
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Thyroid hormone has been shown to modulate the gene expression of cardiac potassium channels, however, it is not known if gene expression is different between the atrium and the ventricle. The long-term effects of thyroid hormone on nuclear thyroid hormone receptors are also not known. Triiodothyronine (T3) at 25 μg/100 g of body weight or propylthiouracil (PTU) at 4 mg/100 g of body weight was given to adult rats via a gastric tube for 14 days. The levels of mRNA of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2, erg, LQT1, and minK were assayed by RNase protection assay. The mRNA of nuclear T3-receptor-α1 and T3-receptor-β1 were also assayed for 15 days. After T3 (or PTU), plasma free T3 and free T4 increased (or decreased) significantly. The mRNA levels of Kv1.2 and Kv1.4 were reduced after T3 in the atrium and the ventricle, while PTU increased the levels in both chambers. Kv1.5 was significantly up-regulated by T3 in the atrium and the ventricle (P<0.02 for both) and PTU decreased its expression in the ventricle (P<0.02). Kv2.1 and Kv4.2 were not affected by T3 or PTU. mRNA of erg was not affected by T3 in the atrium but decreased in the ventricle (P<0.01). After PTU, erg mRNA was decreased in the atrium (P<0.02) but increased in the ventricle (P<0.01). LQT1 was decreased by T3 in both chambers (P<0.01) and not affected by PTU. minK was not detectable in the control state and was up-regulated only in the atrium: a peak on the 4th day followed by a decline to the undetectable level on the 10-15th days. During T3 treatment, nuclear T3-receptor-α1 and β1 mRNA were decreased in the initial 3 days but returned to control levels thereafter. Conclusions: Between the atrium and ventricle of the adult rat heart, the responses of gene expression of voltage-gated potassium channels to T3 or PTU were quantitatively or qualitatively different and the differential responses may explain cardiac manifestations of hyperthyroidism, which is a frequent complication of supraventricular arrhythmia.
- Japanese Heart Journal Associationの論文
著者
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AIZAWA Yoshifusa
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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Watanabe Kenichi
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences
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Hosaka Yukio
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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Watanabe Hiroshi
Division of Infectious Diseases, Department of Infectious Medicine, Kurume University School of Medi
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Komura Satoru
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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Komura Satoru
新潟大学 医歯学総合研究科循環器学
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Ma Mei
Department of Clinical Pharmacology, Niigata College of Pharmacology
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Yamamoto Tadashi
Renal Research Institute Graduate School of Medical and Dental Science, Niigata University
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Watanabe Kenichi
Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmac
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Aizawa Yoshifusa
Division Of Cardiology First Department Of Internal Medicine Niigata University Graduate School Of M
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Watanabe Hiroshi
Division Of Cardiology Hemotology And Endocrinology Niigata University Graduate School Of Medical And Dental Science
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Komura Satoru
Division of Cardiology Graduate School of Medical and Dental Science, Niigata University
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Hosaka Yukio
Division of Cardiology Graduate School of Medical and Dental Science, Niigata University
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