Thyroid control of sarcolemmal Na+/Ca2+ exchanger and SR Ca2+ ATPase in developing rat heart
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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.
- MeSH
- Ca2+-ATPasy biosyntéza MeSH
- genetická transkripce účinky léků MeSH
- hypertyreóza chemicky indukované metabolismus patofyziologie MeSH
- hypotyreóza chemicky indukované metabolismus patofyziologie MeSH
- krysa rodu Rattus MeSH
- membránové proteiny metabolismus MeSH
- messenger RNA biosyntéza MeSH
- myokard metabolismus MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- propylthiouracil farmakologie MeSH
- proteiny vázající vápník biosyntéza MeSH
- pumpa pro výměnu sodíku a vápníku biosyntéza MeSH
- regresní analýza MeSH
- sarkolema metabolismus MeSH
- sarkoplazmatické retikulum enzymologie MeSH
- srdce růst a vývoj MeSH
- štítná žláza fyziologie MeSH
- trijodthyronin farmakologie MeSH
- vývojová regulace genové exprese * účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Ca2+-ATPasy MeSH
- membránové proteiny MeSH
- messenger RNA MeSH
- phospholamban MeSH Prohlížeč
- propylthiouracil MeSH
- proteiny vázající vápník MeSH
- pumpa pro výměnu sodíku a vápníku MeSH
- trijodthyronin MeSH