Genomic and non-genomic regulation of L-type calcium channels in rat ventricle by thyroid hormone.
Hyperthyroidism is associated with low exercise tolerance despite high cardiac output and sometimes with the development of heart failure. L-type calcium channels may play a role in the mechanism, but this has not been fully understood. We examined the effects of thyroid hormone on gene expression and function of L-type calcium channels in rat ventricles by the ribonuclease protection assay and whole-cell patch-clamp technique, respectively. The effects of bisoprolol, beta-blocking agent, on the regulation of calcium channel by thyroid hormone was also studied. In hyperthyroid animals, the mRNA of the calcium channel alpha1c subunit was reduced on day 4, compared with that in euthyroid animals, and remained low on day 8. Bisoprolol did not affect the thyroid hormone mediated decrease in alpha1c subunit mRNA. While L-type calcium current was greater in hyperthyroid than euthyroid myocytes on day 4, it was smaller on day 8. In addition, the isoproterenol-induced increase in calcium current in euthyroid rats was attenuated in hyperthyroid rats. Acetylcholine decreased calcium current in hyperthyroid myocytes, but not in euthyroid myocytes. In conclusion, L-type calcium current was increased by thyroid hormone in rat ventricular myocytes by the activation of the adenylate cyclase cascade, despite a decreased calcium channel gene expression. These genomic and non-genomic modifications may play an important role in the association of high cardiac output with low exercise tolerance, and in the development of heart failure in hyperthyroidism.
Watanabe
Hiroshi
H
Division of Cardiology, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan. hiroshi7@med.niigata-u.ac.jp
Washizuka
Takashi
T
Komura
Satoru
S
Yoshida
Tsuyoshi
T
Hosaka
Yukio
Y
Hatada
Katsuharu
K
Aizawa
Yoshifusa
Y
Chinushi
Masaomi
M
Yamamoto
Tadashi
T
Ma
Meilei
M
Watanabe
Kenichi
K
D000109:Acetylcholine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017298:Bisoprolol / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000502:physiology; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism*; D006980:Hyperthyroidism / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014284:Triiodothyronine / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D014284:Triiodothyronine; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D000109:Acetylcholine; D017298:Bisoprolol