Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nishiyama
A
A
Department of Circulation, Nagoya University, Japan.
Kambe
F
F
Kamiya
K
K
Seo
H
H
Toyama
J
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D015152:Blotting, Northern; D006332:Cardiomegaly / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000378:metabolism* / Q000502:physiology; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015221:Potassium Channels; D020033:Protein Isoforms; D012333:RNA, Messenger; D014284:Triiodothyronine; D011433:Propranolol; D018995:Myosin Heavy Chains; D007545:Isoproterenol; D013974:Thyroxine