3,5,3 '-triiodothyronine deprivation affects phenotype and intracellular [Ca2+](i) of human cardiomyocytes in culture

Objective: A decrease in plasma T3 concentration is a frequent finding in p atients with heart failure. However, the role of this 'low T3 syndrome' on disease evolution has never been clarified. As phenotypic and functional ca rdiomyocyte impairments are alterations that correlate with the failing myo cardium, we studied the long-term effects of T3 deprivation on human cardio myocyte structure and calcium handling. Methods: Atrial cardiomyocytes and myocardial tissue were cultured with or without 3 nM T3. Microscopical exam ination of structural features was followed by analysis of alpha -sarcomeri c actinin and sarcoplasmic reticulum calcium ATP-ase (SERCA-2) content. Cal cium handling was studied by [Ca2+](i) imaging. Results: When stimulated wi th cyclopiazonic acid, a SERCA-2 inhibitor, T3-deprived cardiomyocytes show ed significantly faster (P=0.03) and more transient (P=0.04) increases in [ Ca2+](i) than T3-supplemented cells. Moreover, in the T3-free cultures a si gnificantly lower number of cells (P=0.003) responded to caffeine, a typica l activator of sarcoplasmic reticulum Ca2+-release channel. T3-deprived car diomyocytes also presented altered morphology with larger dimensions than T 3-supplemented cells (P <0.0001). Additionally, in T3-deprived samples a-sa rcomeric actinin and SERCA-2 protein levels were reduced to 65.6 +/-3% (P < 0.0001) and 74.1 +/-4% (P=0.005), respectively, when compared with the T3-s upplemented group. Conclusions: Our data show that human cardiomyocyte calc ium handling and phenotype are strongly influenced by T3 suggesting importa nt implications of the 'low T3 syndrome' on the progression of heart failur e. (C) 2001 Elsevier Science BY All rights reserved.