Nishiyama A, Kambe F, Kamiya K, Seo H, Toyama J
Department of Circulation, Nagoya University, Japan.
Cardiovasc Res. 1998 Nov;40(2):343-51. doi: 10.1016/s0008-6363(98)00135-7.
Thyroid hormone modifies cardiac action potentials and outward potassium currents directly and indirectly e.g. through beta-adrenergic signaling pathway. We thus examined the expression of six voltage-gated potassium channel alpha-subunits in the rat left ventricle under hypo- and hyperthyroid status, and tested roles of beta-adrenergic signaling pathway in their expressions under both status.
Hypothyroidism and hyperthyroidism were induced by administration of methimazole (MMI) for 4 weeks and by injection of L-thyroxine (T4) to the MMI-treated rats for the last 7 days, respectively. To distinguish the effects of T4 and the beta-adrenergic system, propranolol (Pro) was administered to the MMI-treated rats together with T4, and isoproterenol (Iso) was injected to MMI-treated rats for the last 7 days. The mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 in the left ventricles were determined by ribonuclease protection assay.
MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n = 6, p < 0.05). T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n = 6, p < 0.05). Kv4.2 mRNA level was restored to the control level by T4. In contrast, the Kv1.2 and Kv1.4 mRNA levels increased in hypothyroid rats (161% and 186% of control value, respectively; n = 6, p < 0.01) and decreased in hyperthyroid rats (14% and 33% of control value, respectively; n = 6, p < 0.01). The Kv4.3 mRNA level was not altered by thyroid status. Pro did not inhibit the T4-induced hypertrophy. Iso induced cardiac hypertrophy. Pro or Iso by itself did not alter Kv mRNA levels except for Kv1.2, the message of which was decreased by Iso.
Thyroid hormone differentially regulates the expression of Kv1.4, Kv1.5, Kv2.1 and Kv4.2 mRNA levels in the rat left ventricle. This effect is not mediated through beta-adrenergic signaling pathway. On the other hand, the reduction in Kv1.2 mRNA level was associated with cardiac hypertrophy induced by T4 or Iso.
甲状腺激素可直接或间接（如通过β-肾上腺素能信号通路）改变心脏动作电位和外向钾电流。因此，我们检测了甲状腺功能减退和亢进状态下大鼠左心室中六种电压门控钾通道α亚基的表达，并测试了β-肾上腺素能信号通路在这两种状态下对其表达的作用。
分别通过给予甲巯咪唑（MMI）4周诱导甲状腺功能减退，以及在MMI处理的大鼠最后7天注射L-甲状腺素（T4）诱导甲状腺功能亢进。为区分T4和β-肾上腺素能系统的作用，将普萘洛尔（Pro）与T4一起给予MMI处理的大鼠，并在MMI处理的大鼠最后7天注射异丙肾上腺素（Iso）。通过核糖核酸酶保护试验测定左心室中Kv1.2、Kv1.4、Kv1.5、Kv2.1、Kv4.2和Kv4.3的mRNA水平。
MMI处理诱导甲状腺功能减退，导致Kv1.5、Kv2.1和Kv4.2的mRNA水平显著降低（分别为对照值的19%、77%和61%；n = 6，p < 0.05）。给予T4诱导甲状腺功能亢进和心脏肥大，并使Kv1.5和Kv2.1的mRNA水平高于对照值（分别为212%和140%；n = 6，p < 0.05）。T4使Kv4.2的mRNA水平恢复到对照水平。相反，Kv1.2和Kv1.4的mRNA水平在甲状腺功能减退的大鼠中升高（分别为对照值的161%和186%；n = 6，p < 0.01），在甲状腺功能亢进的大鼠中降低（分别为对照值的14%和33%；n = 6，p < 0.01）。Kv4.3的mRNA水平不受甲状腺状态的影响。Pro不抑制T4诱导的肥大。Iso诱导心脏肥大。Pro或Iso单独使用除了Kv1.2外，不改变Kv mRNA水平，Iso可降低Kv1.2的mRNA水平。
甲状腺激素对大鼠左心室中Kv1.4、Kv1.5、Kv2.1和Kv4.2 mRNA水平的表达有差异调节作用。这种作用不是通过β-肾上腺素能信号通路介导的。另一方面，Kv1.2 mRNA水平的降低与T4或Iso诱导的心脏肥大有关。
