Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?

Abstract

Previous studies have reported the existence of skeletal muscle fibers that coexpress multiple myosin heavy chain isoforms. These surveys have usually been limited to studying the polymorphic profiles of skeletal muscle fibers from a limited number of muscles (i.e., usually <4). Additionally, few studies have considered the functional implications of polymorphism. Hence, the primary objective of this study was to survey a relatively large number of rat skeletal muscle/muscle regions and muscle fibers ( n≈ 5,000) to test the hypothesis that polymorphic fibers represent a larger fraction of the total pool of fibers than do so-called monomorphic fibers, which express only one myosin heavy chain isoform. Additionally, we used Hill's statistical model of the force-velocity relationship to differentiate the functional consequences of single-fiber myosin heavy chain isoform distributions found in these muscles. The results demonstrate that most muscles and regions of rodent skeletal muscles contain large proportions of polymorphic fibers, with the exception of muscles such as the slow soleus muscle and white regions of fast muscles. Several muscles were also found to have polymorphic profiles that are not consistent with the I↔IIA↔IIX↔IIB scheme of muscle plasticity. For instance, it was found that the diaphragm muscle normally contains I/IIX fibers. Functionally, the high degree of polymorphism may 1) represent a strategy for producing a spectrum of contractile properties that far exceeds that simply defined by the presence of four myosin heavy chain isoforms and 2) result in relatively small differences in function as defined by the force-velocity relationship.

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

“…The results show that single fibers can express more than one MHC isoforms [6][7][8][9]. Thus, fibers from mammals were found to contain variable proportions of MHC hybrids coexpressing, at the protein level, up to four isoforms [10]. This makes up the spectrum of various motor units and sheds light on the plasticity of expression of the MHC gene family as well as on its regulation.…”

Skeletal muscle fiber types in the ghost crab,Ocypode quadrata:implications for running performance

“…Pette and colleagues interpreted these fibers as being transient in nature, being in the process of switching from one fiber type to another (Pette and Staron, 2000;Pette and Staron, 2001). More recently, the common occurrence of these fibers has called this interpretation into question, raising the possibility that these intermediate fibers types provide a continuum of mechanical properties to the muscles (Caiozzo et al, 2003;Medler et al, 2004;Stephenson, 2001). Indeed, single fibers containing two MHC isoforms possess contractile properties intermediate to pure fiber types (Andruchov et al, 2004;Caiozzo, 2002;Caiozzo et al, 2003).…”

“…More recently, the common occurrence of these fibers has called this interpretation into question, raising the possibility that these intermediate fibers types provide a continuum of mechanical properties to the muscles (Caiozzo et al, 2003;Medler et al, 2004;Stephenson, 2001). Indeed, single fibers containing two MHC isoforms possess contractile properties intermediate to pure fiber types (Andruchov et al, 2004;Caiozzo, 2002;Caiozzo et al, 2003). In the case of the mid-region fibers in the extensor and flexor carpopodite, it is unclear what advantage might be gained by the roughly equal expression of two isoforms, rather than expressing a single isoform.…”

Novel murine clonal cell lines either express slow or mixed (fast and slow) muscle markers following differentiation in vitro

“…As myotube formation and differentiation is not completely synchronous, this variation in expression levels of MHC isoforms may represent myotubes at slightly different stages of differentiation. In vivo expression of several adult MHC isoforms in the so-called hybrid fibers has been reported as indicative of a change in phenotype occurring in adult striated muscle (Staron and Pette, 1993;Caiozzo et al, 2003), and during embryogenesis as well (Lyons et al, 1990).…”