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

R. Shenoy, I. Klein, K. Ojamaa

Research output: Contribution to journalArticlepeer-review

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Abstract

Thyroid hormone exerts positive inotropic effects on the heart mediated in part by its regulation of calcium transporter proteins, including sarco-(endo)plasmic reticulum Ca2+-ATPase (SERCA2), phospholamban (PLB), and Na+/Ca2+ exchanger (NCX). To further understand the potential cardiac chamber-specific effects of thyroid hormone action, we compared the triiodo-L-thyronine (T3) responsiveness of calcium transporter proteins in atrial versus ventricular tissues. Rats were rendered hypothyroid by ingestion of propylthiouracil, and a subgroup of animals was treated with T3 for 7 days (7 μg/day by constant infusion). Atrial and left ventricular (LV) tissue homogenates were analyzed for expression of SERCA2, PLB, and NCX proteins by Western blot analysis. SERCA2 protein significantly decreased by 50% in hypothyroid LV and was normalized by T3 treatment. In contrast, SERCA2 protein in atria was unaltered in the hypothyroid state. PLB protein expression significantly increased by 1.6- and 5-fold in the hypothyroid LV and atria, respectively, and returned to euthyroid levels with T3 treatment. Expression of NCX protein showed a greater response to T3 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 atria compared with LV, suggesting that PLB may play a minor role in the regulation of SERCA2 function in normal atria. We conclude that calcium transporter proteins are responsive to thyroid hormone in a chamber-specific manner, with atria showing a greater change in protein content in response to T3. The differential effect on atria may account for the occurrence of atrial rather than ventricular arrhythmias in response to even mild degrees of thyrotoxicosis.

Original languageEnglish
Pages (from-to)H1690-H1696
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number4 50-4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Calcium ATPase
  • Myocytes
  • Phospholamban
  • Sodium/calcium exchanger

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