We performed 2 wk of mechanical overload by synergist ablation on plantaris muscles from a small rodent hibernator, Spermophilus lateralis. While this muscle displays prominent myosin heavy-chain (MyHC) isoform shifts during hibernation, sensitivity to mechanical loading as a stimulus for muscle mass and isoform plasticity has not been demonstrated. Squirrel muscles, whether during hibernation or not, potentially are less sensitive to mechanical unloading, but we hypothesized that increased loading would produce the typical mammalian response of greater plantaris mass and MyHC shifts. Mechanical overload produced a 50% increase in muscle mass but, surprisingly, no changes in MyHC isoform protein or mRNA expression, despite previously observed fast-to-slow MyHC isoform switching during hibernation. Citrate synthase enzyme activity, as well as mRNA expression of creatine kinase and the muscle growth factor myostatin, were all unchanged. The mRNA expression of critical muscle atrophy genes decreased by 50% during hypertrophy, including ubiquitin ligases MuRF1 and MAFbx, and the related transcription factor FOXO-1a. Insulin-like growth factor (IGF-1) and hypoxia-inducible factor (HIF-1alpha) mRNA expression was elevated by 400% and 150%. Fast-to-slow MyHC isoform shifts appear unnecessary to support the increased recruitment of the plantaris muscle, shifts which are seen in other rodent models. Our results are consistent with muscular activity during interbout arousals as a potential mechanism to preserve muscle mass, but illustrate the primary importance of other seasonal factors besides patterns of muscle activation which must act in concert to alter MyHC isoforms and muscle fiber type during hibernation.
Hibernating ground squirrels do not show slow to fast myosin heavy‐chain (MyHC) isoform transitions with atrophy, and we test whether increased muscle loading would also fail to produce typical MyHC isoform shifts. Field‐caught, Summer‐active ground squirrels (Spermophilus lateralis) were assessed for the responsiveness of hindlimb plantaris muscles to mechanical overload through synergist surgical ablation. Plantaris muscles of surgical animals were 40% larger than controls after 14 days, but did not show any of the expected shifts in MyHC isoform expression. We also measured MyHC isoform mRNA expression, citrate synthase activity, and the expression of a suite of genes involved in the control of skeletal muscle mass and MyHC isoform expression, including MAFbx, MuRF1, FOXO1, IGF1 and IGFBP5, and myostatin. Our results show an unusual insensitivity of hibernator muscles to mechanical overload induced isoform shifts, yet muscle mass was increased, which has implications for isoform expression and muscle adaptations during hibernation. Funding sources: NIH SCORE, NIH RISE, CSULB.
Hibernating ground squirrels demonstrate a greatly reduced, or even an absence of, atrophy in a variety of skeletal muscles and the heart during 4‐6 months of winter dormancy. We test whether these muscles are equally insensitive to inactivity induced reductions in muscle mass and changes in myosin heavy‐chain (MyHC) isoform expression. Field‐caught ground squirrels were captured during their Summer‐active periods, and subjected to cage restriction (small, individual and larger, group cages). Soleus, plantaris, medial and lateral gastrocnemius, diaphragm and cardiac muscles were studied for changes in muscle mass, MyHC isoform expression, citrate synthase activity, and atrophy related genes. Citrate synthase activity and mass was unchanged in all skeletal muscles and the heart. Cardiac alpha MyHC isoform expression was significantly increased in cage‐restricted animals. MAFbx, MuRF1, FOXO1, IGF1 and IGFBP5, and myostatin mRNA expression were also determined through RT‐PCR. The results demonstrate that activity restriction does not significantly alter skeletal muscle mass or MyHC isoform expression even in non‐hibernating ground squirrels and mechanistically suggests that protection during hibernation is an intrinsic adaptation. Funding sources: NIH SCORE, NIH RISE, CSULB.
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