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 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 microg/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.
Cernohorský
J
J
Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic.
Kolár
F
F
Pelouch
V
V
Korecky
B
B
Vetter
R
R
D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000254:growth & development*; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D012508:Sarcolemma / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D008565:Membrane Proteins; D011441:Propylthiouracil; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D014284:Triiodothyronine; D000099211:Phospholamban