Is functional hypertrophy and specific force coupled with the addition of myonuclei at the single muscle fiber level? - PubMed (original) (raw)

Is functional hypertrophy and specific force coupled with the addition of myonuclei at the single muscle fiber level?

Rizwan Qaisar et al. FASEB J. 2012 Mar.

Abstract

Muscle force is typically proportional to muscle size, resulting in constant force normalized to muscle fiber cross-sectional area (specific force). Mice overexpressing insulin-like growth factor-1 (IGF-1) exhibit a proportional gain in muscle force and size, but not the myostatin-deficient mice. In an attempt to explore the role of the cytoplasmic volume supported by individual myonuclei [myonuclear domain (MND) size] on functional capacity of skeletal muscle, we have investigated specific force in relation to MND and the content of the molecular motor protein, myosin, at the single muscle fiber level from myostatin-knockout (Mstn(-/-)) and IGF-1-overexpressing (mIgf1(+/+)) mice. We hypothesize that the addition of extra myonuclei is a prerequisite for maintenance of specific force during muscle hypertrophy. A novel algorithm was used to measure individual MNDs in 3 dimensions along the length of single muscle fibers from the fast-twitch extensor digitorum longus and the slow-twitch soleus muscle. A significant effect of the size of individual MNDs in hypertrophic muscle fibers on both specific force and myosin content was observed. This effect was muscle cell type specific and suggested there is a critical volume individual myonuclei can support efficiently. The large MNDs found in fast muscles of Mstn(-/-) mice were correlated with the decrement in specific force and myosin content in Mstn(-/-) muscles. Thus, myostatin inhibition may not be able to maintain the appropriate MND for optimal function.

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Figures

Figure 1.

Figure 1.

Confocal images of single muscle fibers and representative images of myonuclei shape in control (A, D), _Mstn_−/− (B, E) and IGF-1-overexpressing mice (C, F) in EDL (A–C) and soleus (D–F) fibers. DAPI (blue) stained myonuclei and rhodamine phalloidin (red)-labeled actin. Scale bars = 50 μm (fiber); 3 μm (nuclei).

Figure 2.

Figure 2.

Box plots show

sd

of MND sizes from individual muscle fiber segments from EDL (A) and soleus (B) muscles. Boxes represent 25th and 75th percentiles; median value is indicated as a band near the middle of the box. Horizontal bars denote the 10th and 90th percentiles; data outside this range are indicated as dots.

Figure 3.

Figure 3.

Enzyme histochemical myofibrillar ATPase, pH 4.5, (A–C) and SDH (D–F) staining of soleus muscle cross-sections from control (A, D), _Mstn_−/− (B, E), and mIgf1+/+ (C, F) mice, respectively. Muscle fiber types I and IIa are shown. Scale bar = 50 μm.

Figure 4.

Figure 4.

Average single muscle fiber MND vs. fiber CSA in single EDL (A) and type I soleus (B) and type IIa soleus (C) muscle fibers from control (solid circles, solid line), _Mstn_−/− (open circles, dashed line), and mIgf1+/+ (open triangles, dotted line) mice.

Figure 5.

Figure 5.

Single muscle fiber absolute force (A), specific force (B), and stiffness (C) together with myosin content, described as percentage (D). Results from single muscle fibers expressing the type IIb MyHC isoform in the EDL and the IIa MyHC isoform in the soleus are included. Values are means ±

se.

*P < 0.05 vs. control; 1-way ANOVA.

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