Maximal ATPase activity and calcium sensitivity of reconstituted myofilaments are unaltered by the fetal troponin T re-expressed during human heart failure

Re-expression of a fetal isoform of troponin T (TnT₄) has been demonstrated in failing human ventricular myocardium and associated with a decrease in myofibrillar ATPase activity. In order to elucidate the regulatory role of the re-expressed TnT₄ in the failing human heart, we measured ATPase activity in reconstituted cardiac myofilaments prepared with recombinant human TnT₄ or the adult human isoform of troponin T (TnT₃). Neither the maximal calcium-activated ATPase activity nor the calcium sensitivity of this biochemical assay was significantly different between reconstituted myofilaments containing adult TnT₃ or fetal TnT₄. Our results suggest that the re-expressed fetal TnT₄ is not responsible for the depressed ATPase activity of failing ventricular myofibrils. The increased expression of the fetal isoform of this thin filament regulatory protein in the failing ventricle may be a consequence of a programmed change in gene expression occurring in response to hemodynamic stress, but probably does not contribute to depressed ventricular function characteristic of dilated cardiomyopathies.