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Published on: September 10, 2015
Thyroid control of sarcolemmal Na+/Ca2+ exchanger and SR Ca2+-ATPase in developing rat heart
J Cernohorský1, F Kolár, V Pelouch
1Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic.
Insights
Postnatal thyroid hormone levels are crucial for heart calcium handling. Hypothyroidism increases sarcolemmal Na+/Ca2+ exchanger (NCX) and decreases SR Ca2+-ATPase (SERCA2), while hyperthyroidism shows opposite functional changes without altering protein expression.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormone (TH) is vital for postnatal heart maturation, influencing myocardial calcium handling.
- During development, sarcolemmal (SL) Na+/Ca2+ exchanger (NCX) function decreases as sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) function increases.
Purpose of the Study:
- To investigate the impact of postnatal hypothyroidism and hyperthyroidism on myocardial NCX and SERCA2 expression and function in rats.
- To elucidate the role of thyroid hormone in regulating key proteins involved in cardiac calcium homeostasis during development.
Main Methods:
- Induction of hypothyroidism and hyperthyroidism in rat pups via drug administration.
- Analysis of NCX and SERCA2 mRNA and protein levels using Northern and Western blotting.
- Assessment of SL Na+ gradient-induced and SR Ca2+ transport activities in isolated cardiac membranes.
Main Results:
- Hypothyroidism led to increased NCX (mRNA: +66%, protein: +80%) and decreased SERCA2 (mRNA: -55%, protein: -70%) with corresponding functional changes (P < 0.05).
- Hyperthyroidism resulted in reduced NCX activity (-50%) and elevated SERCA2 activity (+150%) (P < 0.05), despite unchanged protein expression.
- Functional changes in hyperthyroidism are likely due to altered phospholamban phosphorylation, not changes in NCX/SERCA2 expression.
Conclusions:
- Physiological thyroid hormone levels are essential for the normal reciprocal developmental changes in myocardial NCX and SERCA2 expression and function.
- Thyroid hormone regulates cardiac calcium handling proteins, impacting contractility and relaxation during the postnatal period.
- Altered thyroid status during development can disrupt cardiac calcium cycling, with implications for heart function.
Abstract:
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.
