cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform

Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium-dependent myocardial force development, are expressed in the human; they differ in charge and length. Their expression is regulated developmentally and is affected by disease states. Human cTnT (hcTnT) isoform effects have been examined in reconstituted myofilaments. In this study, we evaluated the modulatory effects of overexpressing one cTnT isoform on in vitro and in vivo myocardial function. A hcTnT isoform, hcTnT1, expressed during development and in heart disease but not in the normal adult heart, was expressed in transgenic (TG) mice (1–30% of total cTnT). Maximal active tension measured in skinned myocardium decreased as a function of relative hcTnT1 expression. The pCa at half-maximal force development, Hill coefficient, and rate of redevelopment of force did not change significantly with hcTnT1 expression. In vivo maximum rates of rise and fall of left ventricular pressure decreased, and the half-time of isovolumic relax...