Microgravity-induced transformations of myosin isoforms and contractile properties of skeletal muscle

This study examined the effects of microgravity (14 days) on 1) the contractile properties of the soleus (Sol), an antigravity skeletal muscle; and 2) the myosin heavy chain (MHC) protein and mRNA isoform content of the Sol, vastus intermedius (VI), plantaris (Plan), and tibialis anterior (TA) muscles. The force-velocity relationships of the flight Sol muscles had a significant reduction in maximal isometric tension (-37%) and a corresponding increase in maximal shortening velocity (+20%). Additionally, the force-frequency relationship of the flight Sol muscles was shifted to the right of the ground-based control group. Microgravity had the greatest effect on muscle fiber composition in the Sol muscle, with a reduction in slow muscle fibers and a corresponding increase in muscle fibers categorized as hybrid fibers. The estimated absolute MHC isoform content was altered to the greatest extent in the Sol and VI muscles, with significant decreases and elevations in the slow type I and fast type IIX MHC protein isoforms, respectively. Consistent with the protein data, both the flight Sol and VI muscles exhibited significant elevations in the fast type IIX MHC mRNA isoform. In contrast, however, the flight Plan and TA groups had significant increases in the fast type IIB MHC mRNA isoform content without corresponding changes at the protein level. The results of this study suggest that spaceflight of even short duration produces important changes in the contractile properties of antigravity skeletal muscle. These changes are mediated by alterations in MHC phenotype and reductions in muscle mass. In some instances, the alterations in MHC mRNA isoform content seemed to be uncoupled from those occurring at the protein level. This apparent uncoupling between mRNA and protein expression demonstrates that the effects of microgravity must be better understood at the transcriptional, translational, and post-translational levels.