Abe A, Yamamoto T, Isome M, Ma M, Yaoita E, Kawasaki K, Kihara I, Aizawa Y
First Department of Internal Medicine, Institute of Nephrology, Niigata University School of Medicine, Niigata, Japan.
Biochem Biophys Res Commun. 1998 Apr 7;245(1):226-30. doi: 10.1006/bbrc.1998.8411.
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.
甲状腺激素对心脏功能或节律的影响已为人所知;然而,其机制仍不清楚。在本研究中,由于推测钾通道可调节心脏功能,因此检测了三碘甲状腺原氨酸(T3)对大鼠心脏电压门控钾通道基因表达的影响。通过核糖核酸酶保护试验检测了用T3或丙硫氧嘧啶(PTU)处理的大鼠心脏中五个电压门控钾通道基因α亚基(Kv1.2、Kv1.4、Kv1.5、Kv2.1和Kv4.2)的mRNA表达。除Kv1.4 mRNA外,所有这些基因在正常大鼠心室中均有明显表达。T3处理可显著抑制心室中Kv1.2 mRNA的表达,而PTU处理则可增强其表达。有趣的是,PTU处理可同时诱导心室中Kv1.4 mRNA表达上调和Kv1.5 mRNA表达下调。此外,T3替代可恢复PTU诱导的心室Kv1.5 mRNA表达下调。T3或PTU处理未观察到心室中Kv2.1和Kv4.2 mRNA表达的变化。在心脏心房中也观察到了相同的结果。T3处理也可使对照大鼠心房中可检测到的Kv1.4 mRNA表达显著降低。相比之下,T3处理未诱导大鼠脑中Kv1.2、Kv1.4和Kv1.5 mRNA表达的变化。这些发现表明,甲状腺激素通过共同的T3受体介导的转录水平调控,特异性地影响大鼠心脏中与Shaker相关钾通道基因的mRNA表达。