Stretch activation kinetics were investigated in skinned mouse skeletal muscle fibers of known myosin heavy chain (MHC) isoform content to assess kinetic properties of different myosin heads while generating force. The time to peak of stretch-induced delayed force increase (t(3)) was strongly correlated with MHC isoforms [t(3) given in ms for fiber types containing specified isoforms; means +/- SD with n in parentheses: MHCI 680 +/- 108 (13), MHCIIa 110.5 +/- 10.7 (23), MHCIIx(d) 46.2 +/- 5.2 (20), MHCIIb 23.5 +/- 3.3 (76)]. This strong correlation suggests different kinetics of force generation of different MHC isoforms in the following order:MHCIIb > MHCIIx(d) > MHCIIa >> MHCI. For rat, rabbit, and human skeletal muscles the same type of correlation was found previously. The kinetics decreases slightly with increasing body mass. Available amino acid sequences were aligned to quantify the structural variability of MHC isoforms of different animal species. The variation in t(3) showed a correlation with the structural variability of specific actin-binding loops (so-called loop 2 and loop 3) of myosin heads (r = 0.74). This suggests that alterations of amino acids in these loops contribute to the different kinetics of myosin heads of various MHC isoforms.
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