Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats

Y. Minatoya, K. Ito, Y. Kagaya, Y. Asaumi, M. Takeda, M. Nakayama, J. Takahashi, A. Iguchi, K. Shirato, H. Shimokawa

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Aim: Chronic cardiac unloading causes a time-dependent upregulation of phospholamban (PLB) and depression of myocyte contractility in normal rat hearts. As thyroid hormone is known to decrease PLB expression, we examined whether thyroid hormone restores the depressed contractile performance of myocytes from chronically unloaded hearts. Methods: Cardiac unloading was induced by heterotopic heart transplantation in isogenic rats for 5 weeks. Animals were treated with either vehicle or physiological treatment dose of 3,5,3′-triiodo-l-thyronine (T3) that does not cause hyperthyroidism for the last 3 weeks (n = 20 each). Results: In vehicle-treated animals, myocyte relaxation and [Ca2+]i decay were slower in unloaded hearts than in recipient hearts. Myocyte shortening in response to high [Ca 2+]o was also depressed with impaired augmentation of peak-systolic [Ca2+]i in unloaded hearts compared with recipient hearts. In vehicle-treated rats, protein levels of PLB were increased by 136% and the phosphorylation level of PLB at Ser16 were decreased by 32% in unloaded hearts compared with recipient hearts. By contrast, in the T3-treated animals, the slower relaxation, delayed [Ca2+]i decay, and depressed contractile reserve in myocytes from unloaded hearts were all returned to normal levels. Furthermore, in the T3-treated animals, there was no difference either in the PLB protein level or in its Ser16-phosphorylation level between unloaded and recipient hearts. Conclusion: These results suggest that the treatment with physiological treatment dose of thyroid hormone rescues the impaired myocyte relaxation and depressed contractile reserve at least partially through the restoration of PLB protein levels and its phosphorylation state in chronically unloaded hearts.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalActa Physiologica
Volume189
Issue number3
DOIs
Publication statusPublished - 2007 Mar

Keywords

  • Calcium handling
  • Cardiac myocytes
  • Phospholamban
  • Thyroid hormone
  • Transplantation

ASJC Scopus subject areas

  • Physiology

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