Myosin‐actin cross‐bridge kinetics explain variation in single skeletal muscle fiber function in humans

Abstract

Our objective was to determine if myosin-actin cross-bridge kinetics, measured in their intact myofilament lattice, could account for variation in skeletal muscle fiber type specific performance among healthy and diseased humans. We applied small amplitude sinusoidal analysis for the first time to human skeletal muscle fibers obtained from 9 heart failure patients and 6 controls of similar age and activity level. In both groups, myosin heavy chain (MHC) isoform contractile velocity (I<IIA<IIX) was inversely related to myosin-actin attachment time (ton). The rate of myosin transition between weakly- and strongly-bound states (2πb) increased with MHC velocity, suggesting the myosin-actin detachment time (toff) decreases with faster contractions. These results suggest that total myosin-actin cycle time (ton + toff) decreases with contractile velocity due to reductions in both ton and toff in humans. Heart failure patients had an increased ton, which compensated for their reduced cross-bridge number due to MHC content loss, resulting in similar isometric tensions compared to healthy controls. Collectively, these results indicate the usefulness of cross-bridge kinetics and highlight their potential use for examining the effects of disease, muscle activity and aging on single fiber function. Support: NIH HL-077418 and AG-031303