Differential regulation of SR calcium transporters by thyroid hormone in rat atria and ventricles

Thyroid hormone exerts positive inotropic effects on the heart mediated in part by its regulation of calcium transporter proteins, including sarco(end o)plasmic reticulum Ca2+-ATPase (SERCA2), phospholamban (PLB), and Na+/Ca2 exchanger (NCX). To further understand the potential cardiac chamber-speci fic effects of thyroid hormone action, we compared the triiodo-L-thyronine (T-3) responsiveness of calcium transporter proteins in atrial versus ventr icular tissues. Rats were rendered hypothyroid by ingestion of propylthiour acil, and a subgroup of animals was treated with T-3 for 7 days (7 mug/day by constant infusion). Atrial and left ventricular (LV) tissue homogenates were analyzed for expression of SERCA2, PLB, and NCX proteins by Western bl ot analysis. SERCA2 protein significantly decreased by 50% in hypothyroid L V and was normalized by T-3 treatment. In contrast, SERCA2 protein in atria was unaltered in the hypothyroid state. PLB protein expression significant ly increased by 1.6- and 5-fold in the hypothyroid LV and atria, respective ly, and returned to euthyroid levels with T-3 treatment. Expression of NCX protein showed a greater response to T-3 treatment in atria tissue than in ventricular tissue. Sarcoplasmic reticulum calcium cycling is determined in part by the ratio of SERCA2 to PLB. This ratio was sixfold higher in the a tria compared with LV, suggesting that PLB may play a minor role in the reg ulation of SERCA2 function in normal atria. We conclude that calcium transp orter proteins are responsive to thyroid hormone in a chamber-specific mann er, with atria showing a greater change in protein content in response to T -3. The differential effect on atria may account for the occurrence of atri al rather than ventricular arrhythmias in response to even mild degrees of thyrotoxicosis.