Abstract

**Background:** Calcium (Ca²⁺) homeostasis is fundamental to cardiomyocyte function, with gene expression regulating Ca²⁺ handling being critical for cardiac contractility and adaptation. This study investigates the effects of voluntary wheel training (VWT), a model of physiological cardiac stress, on the expression of key Ca²⁺-regulating genes in rat myocardium, with a specific focus on the modulatory role of thyroid hormones (THs). Given that THs are known regulators of cardiac gene expression and cellular metabolism, their interaction with exercise-induced signaling pathways is highly relevant to cell biology and membrane transport. **Methods:** Male Wistar rats were subjected to VWT for a defined period, with a subset receiving pharmacological manipulation of TH levels. Gene expression of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a), ryanodine receptor (RyR2), and phospholamban (PLN) was quantified in myocardial tissue. **Results:** VWT significantly altered the expression profile of Ca²⁺-handling genes, notably increasing SERCA2a/PLN ratio, suggesting enhanced Ca²⁺ reuptake efficiency. This effect was found to be partially or fully dependent on euthyroid status, as TH manipulation significantly attenuated the exercise-induced changes. **Conclusion:** These findings highlight a critical role for THs in mediating the adaptive transcriptional response of the myocardium to exercise, specifically in maintaining Ca²⁺-cycling integrity, which is essential for membrane excitability and cellular signaling in cardiac health.