THYROID CONTROL OF SARCOLEMMAL NA+ CA2+ EXCHANGER AND SR CA2+-ATPASE IN DEVELOPING RAT-HEART/

Thyroid hormone (TH) levels increase in the postnatal life and are ess ential for maturation of myocardial Ca2+ handling. During this time, t he sarcolemmal (SL) Na+/Ca2+ exchanger (NCX) function decreases and th e sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) function increa ses. We examined the effects of postnatal hypo- or hyperthyroidism on NCX and SERCA2 in rat heal ts. 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 in jections of 10 mu g/100 g body weight of 3,3',5-triiodo-L-thyronine du ring this period. Ventricular steady-state mRNA and protein levels of NCX and SERCA2 were analyzed by Northern and Western blotting. These w ere compared with SL Na+ gradient-induced and SR oxalate-supported Ca2 + transports in isolated membranes. In hypothyroidism, NCX mRNA and pr otein were elevated by 66 and 80%, respectively, and SERCA2 mRNA and p rotein were reduced to 55 and 70%, respectively (P < 0.05 vs, euthyroi d). Corresponding differences were observed in the respective Ca2+ tra nsports. Conversely, reduced NCX (by 50%) and elevated SERCA2 (by 150% ) activities were found in hyperthyroidism (P < 0.05). The levels of N CX and SERCA2 mRNA and protein were, however, unchanged in hyperthyroi dism, indicating that functional changes are not due to altered NCX an d SERCA2 expression. In this case, a decline in noninhibitory phosphor ylated phospholamban is a likely explanation for the elevated SR Ca2transport. In conclusion, physiological TH levels appear to be essenti al for normal reciprocal changes in the expression and function of myo cardial NCX and SERCA2 during postnatal development.