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Am J Physiol Heart Circ Physiol 275: H264-H273, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 1, H264-H273, July 1998

Thyroid control of sarcolemmal Na+/Ca2+ exchanger and SR Ca2+-ATPase in developing rat heart

Jan Cernohorský1, Frantisek Kolár1, Václav Pelouch1, Borivoj Korecky2, and Roland Vetter3,4

1 Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic; 2 Department of Physiology, University of Ottawa, Ottawa, Canada K1H 8M5; 3 Max Delbrück Center for Molecular Medicine, D-13122 Berlin-Buch, and 4 Institute of Clinical Pharmacology and Toxicology, Free University of Berlin, D-14195 Berlin, Germany

Thyroid hormone (TH) levels increase in the postnatal life and are essential for maturation of myocardial Ca2+ handling. During this time, the sarcolemmal (SL) Na+/Ca2+ exchanger (NCX) function decreases and the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) function increases. We examined the effects of postnatal hypo- or hyperthyroidism on NCX and SERCA2 in rat hearts. Animals were rendered hypothyroid by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from days 2 to 21 postpartum. Hyperthyroidism was induced by daily injections of 10 µg/100 g body weight of 3,3',5-triiodo-L-thyronine during this period. Ventricular steady-state mRNA and protein levels of NCX and SERCA2 were analyzed by Northern and Western blotting. These were compared with SL Na+ gradient-induced and SR oxalate-supported Ca2+ transports in isolated membranes. In hypothyroidism, NCX mRNA and protein were elevated by 66 and 80%, respectively, and SERCA2 mRNA and protein were reduced to 55 and 70%, respectively (P < 0.05 vs. euthyroid). Corresponding differences were observed in the respective Ca2+ transports. Conversely, reduced NCX (by 50%) and elevated SERCA2 (by 150%) activities were found in hyperthyroidism (P < 0.05). The levels of NCX and SERCA2 mRNA and protein were, however, unchanged in hyperthyroidism, indicating that functional changes are not due to altered NCX and SERCA2 expression. In this case, a decline in noninhibitory phosphorylated phospholamban is a likely explanation for the elevated SR Ca2+ transport. In conclusion, physiological TH levels appear to be essential for normal reciprocal changes in the expression and function of myocardial NCX and SERCA2 during postnatal development.

hypothyroidism; hyperthyroidism; immature myocardium; calcium handling; gene expression; phospholamban


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