Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes

T. Zinman, V. Shneyvays, N. Tribulova, M. Manoach, A. Shainberg

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28 Scopus citations


In this study, we examined the acute effects of thyroid hormones (TH) T3 and T4, leading to improvement of myocardial function through activation of Ca2+ extrusion mechanisms and, consequently, prevention of intracellular calcium overload. Extracellular calcium elevation from 1.8 to 3.8 mM caused immediate increase in intracellular calcium level ([Ca2+]i) in newborn cardiomyocyte cultures. Administration of 10 or 100 nM T3 or T4 rapidly (within 10 sec) decreased [Ca2+]i its control level. Similar results were obtained when [Ca2+]i was elevated by decreasing extracellular Na+ concentration, causing backward influx of Ca 2+ through Na+/ Ca2+ exchanger, or by administration of caffeine, releasing Ca2+ from the sarcoplasmic reticulum (SR). Under these conditions, T3 or T4 decreased [Ca2+]i. T3 and T4 also exhibited protective effects during ischemia. T3 or T4 presence during hypoxia for 120 min in culture medium restricted the increase of [Ca 2+]i and prevented the pathological effects of its overload. An inhibitor of SR Ca2+-ATPase (SERCA2a), thapsigargin, increases [Ca2+]i and in its presence neither T 3 nor T4 had any effect on the [Ca2+] i level. The reduction of [Ca2+]i level by T3 and T4 was also blocked in the presence of H-89 (a PKA inhibitor), and by calmodulin inhibitors. The effect of TH on the reduction of [Ca2+]i was prevented by propranolol, indicating that the hormones exert their effect through interaction with adrenergic receptors. These results support our hypothesis that TH prevent calcium overload in newborn rat cardiomyocytes, most likely by a direct, acute, and nongenomic effect on Ca 2+ transport into the SR.

Original languageEnglish
Pages (from-to)220-231
Number of pages12
JournalJournal of Cellular Physiology
Issue number1
StatePublished - Apr 2006


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