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Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes
Author(s) -
Zinman T.,
Shneyvays V.,
Tribulova N.,
Manoach M.,
Shainberg A.
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20562
Subject(s) - thapsigargin , endocrinology , medicine , extracellular , calcium , chemistry , hormone , caffeine , intracellular , calcium in biology , calmodulin , endoplasmic reticulum , biology , biochemistry
In this study, we examined the acute effects of thyroid hormones (TH) T 3 and T 4 , leading to improvement of myocardial function through activation of Ca 2+ 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 ([Ca 2+ ] i ) in newborn cardiomyocyte cultures. Administration of 10 or 100 nM T 3 or T 4 rapidly (within 10 sec) decreased [Ca 2+ ] i to its control level. Similar results were obtained when [Ca 2+ ] i was elevated by decreasing extracellular Na + concentration, causing backward influx of Ca 2+ through Na + /Ca 2+ exchanger, or by administration of caffeine, releasing Ca 2+ from the sarcoplasmic reticulum (SR). Under these conditions, T 3 or T 4 decreased [Ca 2+ ] i . T 3 and T 4 also exhibited protective effects during ischemia. T 3 or T 4 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 Ca 2+ ‐ATPase (SERCA2a), thapsigargin, increases [Ca 2+ ] i and in its presence neither T 3 nor T 4 had any effect on the [Ca 2+ ] i level. The reduction of [Ca 2+ ] i level by T 3 and T 4 was also blocked in the presence of H‐89 (a PKA inhibitor), and by calmodulin inhibitors. The effect of TH on the reduction of [Ca 2+ ] 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. J. Cell. Physiol. 207: 220–231, 2006. © 2005 Wiley‐Liss, Inc.