Regulation of Sarcoplasmic Reticulum Gene Expression

The purpose of this study was to determine the expression of genes encoding sarcoplasmic reticulum proteins responsible for calcium release, uptake and storage during cardiac muscle development with age and cardiac hypertrophy/atrophy induced by the manipulation of thyroid function. New Zealand white rabbits were used as experimental animals. Cardiac muscle exclusively expressed cardiac isoform of ryanodine receptor, Ca2+-ATPase and calsequestrin, and their expression levels were gradually increased from fetal to adult stages examined. In hyperthyroid hearts, the steady-state level of cardiac ryanodine receptor mRNA and cardiac Ca2+-ATPase mRNA were coordinately increased, but decreased in hypothyroidism. In accord with the changes in Ca2+-ATPase mRNA levels, the Ca2+-ATPase protein was also increased in hyperthyroid ventricles and decreased in hypothyroid ventricles. On the other hand, calsequestrin mRNA levels did not change significantly in hyperthyroid and hypothyroid hearts. These results suggest that the rate of calcium release and uptake increased in hyperthyroid hearts and decreased in hypothyroid hearts, even though the amount of Ca2+ cycled is unaltered between different thyroid hormone levels. This study further indicates that the mRNA levels of various sarcoplasmic reticulum proteins responsible for calcium transport are coordinately regulated in response to diverse functional requirements during development and pathophysiological stress.