Thyroid hormone regulation of calcium cycling proteins.

Alterations in thyroid hormone levels have a profound impact on myocardial contractility, speed of relaxation, cardiac output, and heart rate. The mechanisms for these changes include altered expression of several key proteins, involved in the regulation of intracellular calcium homeostasis. Most notably, increases in thyroid hormone and the coordinated increases in cardiac contractile parameters are marked by increases in the levels of the sarcoplasmic reticulum (SR) Ca2+-adenosine triphosphatase (ATPase) and decreases in its inhibitor, phospholamban. These changes at the protein level result in enhanced SR calcium transport and myocyte calcium cycling, leading to increases in the force and rates of contraction as well as relaxation rates at the organ level. However, decreases in thyroid hormone levels are associated with opposite alterations in these two proteins, leading to reduced myocyte calcium handling capacity and lower cardiac contractility. Furthermore, changes in the relative ratio of phospholamban/Ca2+-ATPase correlate with changes in the affinity of the SR Ca2+-transport system and relaxation rates in beating hearts. These findings suggest that thyroid hormone directly regulates SR protein levels and thus, cardiac function.