Introducing fast skeletal muscle troponin T into adult mouse myocardium alongside endogenous cardiac troponin T decreased contractile function and caused chronic myocardial hypertrophy.
Does the co-expression of skeletal and cardiac troponin T decrease cardiac function in a transgenic mouse model?
Myocardial troponin T heterogeneity decreases contractile function, suggesting that TnT homogeneity is necessary for synchronized ventricular contraction.
In contrast to skeletal muscles that simultaneously express multiple troponin T (TnT) isoforms, normal adult human cardiac muscle contains a single isoform of cardiac TnT. To understand the significance of myocardial TnT homogeneity, we examined the effect of TnT heterogeneity on heart function. Transgenic mouse hearts overexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT was investigated in vivo and ex vivo as an experimental system of concurrent presence of two classes of TnT in the adult cardiac muscle. This model of myocardial TnT heterogeneity produced pathogenic phenotypes: echocardiograph imaging detected age-progressive reductions of cardiac function; in vivo left ventricular pressure analysis showed decreased myocardial contractility; ex vivo analysis of isolated working heart preparations confirmed an intrinsic decrease of cardiac function in the absence of neurohumoral influence. The transgenic mice also showed chronic myocardial hypertrophy and degeneration. The dominantly negative effects of introducing a fast TnT into the cardiac thin filaments to produce two classes of Ca(2+) regulatory units in the adult myocardium suggest that TnT heterogeneity decreases contractile function by disrupting the synchronized action during ventricular contraction that is normally activated as an electrophysiological syncytium.
Huang et al. (2007) studied Myocardial TnT heterogeneity. Overexpression of fast skeletal muscle TnT vs. Normal cardiac muscle (endogenous cardiac TnT only) was evaluated on Cardiac function and myocardial contractility. Introducing fast skeletal muscle troponin T into adult mouse myocardium alongside endogenous cardiac troponin T decreased contractile function and caused chronic myocardial hypertrophy.