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While re-expression of the cTnI isoform was seen in the PTU-treated ssTnI TG mouse hearts, fortuitously for us, ssTnI expression http://www.selleckchem.com/products/lee011.html substantially persisted (Fig. 3B). Densitometric estimation of the comparative levels of cTnI:ssTnI (vs. total TnI) in the normal ssTnI TG mice was ?15%:85%, whereas in PTU-treated TG mice, this ratio was ?66%:34%. Thus, while cTnI isoform re-emergence was observed, significant amounts of ssTnI remained in PTU-treated ssTnI TG mice. Next, we examined whether PTU treatment or ssTnI TG expression had any effects on the phosphorylation status of other sarcomeric proteins (Fig. 3C). Pro-Q Diamond staining revealed that the phosphorylation status of other proteins (e.g. cardiac myosin binding protein C, cTnT, tropomyosin, myosin light chain 1 (MLC1), MLC2, or cardiac TnC) was not different in normal and PTU-treated mice. An exception was found in the re-emergence of phospho-cTnI in PTU-treated TG mice, but this was consistent with the ?66% re-emergence of cTnI. For convenience, normal NTG or TG groups will be referred to as ��-MHC(cTnI) or ��-MHC(ssTnI), and PTU-treated NTG or TG groups will be referred to as ��-MHC(cTnI) or ��-MHC(ssTnI), respectively. We sought to characterize the effect of ssTnI expression on myofilament contractile dynamics and determine how http://www.selleck.cn/products/AZD6244.html such effects might be further influenced by a shift in MHC isoform following PTU treatment. A shift from ��-MHC to ��-MHC isoform expression has been shown to slow XB cycling dynamics (Fitzsimons et al. 1998b; Rundell et al. 2005b; Chandra http://www.selleckchem.com/products/bmn-673.html et al. 2007) due to the slower enzymatic rate of the ��-MHC isoform. However, the effect of TnI isoform switching on myofilament contractile dynamics is not well understood. To study these effects, the dynamic force responses to sinusoidal length perturbations of increasing frequency (i.e. chirp protocol, as shown in Fig. 1) were collected from constantly activated muscle fibres from each group of mouse hearts. Contractile dynamic behaviour was approximated using a previously established model (Campbell et al. 2004; Chandra et al. 2007) and fitted model parameters were subsequently used to determine the effects of ssTnI on myofilament contractile dynamics. Model fits were similarly good in ��-MHC(cTnI), ��-MHC(cTnI), ��-MHC(ssTnI), and ��-MHC(ssTnI) groups. R2 values were routinely >0.99, and residuals were normally distributed along the entire range of F(t), providing significant correlations (P