Human skeletal muscle biochemical diversity

Abstract

The molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain, MHC) and mechanosensitive signaling (titin) have been well studied in animals but less is known about their roles in humans. The purpose of this study was to perform a comprehensive analysis of titin, collagen and MHC isoform distributions in a large number of human muscles, to search for common themes and trends in the muscular organization of the human body. In this study, 599 biopsies were obtained from six human cadaveric donors (mean age 83 years). Three assays were performed on each biopsy - titin molecular mass determination, hydroxyproline content (a surrogate for collagen content) and MHC isoform distribution. Titin molecular mass was increased in more distal muscles of the upper and lower limbs. This trend was also observed for collagen. Percentage MHC-1 data followed a pattern similar to collagen in muscles of the upper extremity but this trend was reversed in the lower extremity. Titin molecular mass was the best predictor of anatomical region and muscle functional group. On average, human muscles had more slow myosin than other mammals. Also, larger titins were generally associated with faster muscles. These trends suggest that distal muscles should have higher passive tension than proximal ones, and that titin size variability may potentially act to 'tune' the protein's mechanotransduction capability.

Fig. 1.

(A) Titin molecular mass, (B) collagen content and (C) percentage myosin heavy chain (% MHC) distribution in different anatomical regions of the human (represented by different colors). Shading in C indicates different MHC isoforms. Shading of regions on the human figures represents magnitude, where a lighter shade corresponds to a higher value (higher titin molecular mass, more collagen, greater percentage MHC-1). Note the significant variations across the body and the similarities in titin and collagen trends.

Fig. 2.

(A) Titin molecular mass, (B) collagen content and (C) percentage MHC distribution in muscles with different functions. In some cases, significant differences exist across muscles of different function but correlated trends between different molecular parameters are less clear than in Fig. 1. Abbreviations: Ab, abduction; IR, internal rotation; Fl, flexion; Ex, extension; Ad, adduction; ER, external rotation.

Fig. 3.

Relationships among titin molecular mass and (A) percentage MHC-1, (B) percentage MHC-2A, (C) percentage MHC-2X and (D) collagen content. Dashed lines are linear regression results; collagen content data (μg mg^–1) were log transformed because independent variable data should be normally distributed for linear regression analysis. Note the significant negative correlation between titin mass and percentage MHC-1, which is opposite to that reported for rabbit muscle (Prado et al., 2005).

Fig. 4.

Comparison of MHC percentages for each functional muscle group in the lower extremity. Note that at each joint of the lower extremity there are differences between flexors and extensors opposite to those seen in the rat hindlimb (Eng et al., 2008).