What Is the Basic Contractile Unit of Muscle
Differential splicing of the remarkably numerous (human) exons 363 of the single titin gene (TTN) produces titin isoforms of different lengths (Labeit and Kolmerer, 1995; Bang et al., 2001). Most of the variable splicing is in the titin area, which is located in band I. Long isoforms are more compliant than short isoforms. For example, the conformity of the heart muscle depends on the N2-BA:N2-B ratio, where a higher N2-A prevalence corresponds to a lower resistance to stretching. Genetic ablation of a protein subunit responsible for titin splicing results in large titin molecules that are incredibly compliant in the heart and skeletal muscle (Methawasin et al. 2014). Post-translational modifications, such as phosphorylation and oxidation, can also affect titin compliance, allowing for immediate changes in titin performance (Grutzner et al. 2009; Linke and Kruger, 2010). Sarcomers are the basic contractile units of the heart muscle. They consist of thick and thin filaments, which are essential for the generation and propagation of mechanical forces.
Myosin, the main component of thick filament, consists of MHC subunits and myosin light chain (MLC) subunits. α-MHC (Myh6) and β-MHC (Myh7) are both expressed in the heart during development and in adults. In rodents, β-MHC expression is downregulated after birth, so that in adults, α-MHC is the dominant isoform of MHC in the heart (Lyons et al., 1990; England and Loughna, 2013). MHC isoform switches in response to cardiac stress or hypothyroidism. Pathological hypertrophy is associated with upregulation of β-MHC and downregulation of α-MHC (Krenz and Robbins, 2004; Gupta, 2007). Figure 1 shows the sarcomaer, which is the basic contractile unit of the striated muscle. Sarcomeres are organized in series to form a myofibril. MiRNA-1 and miRNA-133 have been shown to act as specific activators or suppressors of sarcoma formation and muscle gene expression. Deletion of miRNA-1-2 and miRNA-1-1 in mice (miRNA-1 zero) leads to sarcomeric disorders in cardiomyocytes and impaired heart function. All zero miRNA-1 mice died before weaning age (Heidersbach et al., 2013; Wei et al., 2014). miRNA-1 acts to negatively regulate myocardium, the main regulator of smooth muscle gene expression, and telokine, the specific smooth muscle inhibitor of phosphorylation MLC-2 (Heidersbach et al., 2013; Wystub et al., 2013).
The upward regulation of myocardium and telokine in zero miRNA-1 cores may contribute in part to the defect of the sarcoma organization. In addition, studies by Wei et al. have shown that miRNA-1 directly suppresses the estrogen-bound nuclear receptor β (Errβ). The high level of Errβ in the miRNA-1 zero heart activates the expression of genes associated with the fetal sarcoma (Wei et al., 2014). The sarcomere is the basic contractile unit for striated muscle and heart muscle and consists of a complex network of thick filaments, thin filaments and a huge titin protein. A sarcoma is the functional unit (contractile unit) of a muscle fiber. As shown in Figure 2-5, each sarcoma contains two types of myofilaments: thick filaments, which consist mainly of the contractile protein myosin, and thin filaments, which consist mainly of the contractile actin protein. Thin filaments also contain the regulatory proteins troponin and tropomyosin.
When myofilaments are seen under an electron microscope, their arrangement gives the appearance of alternating bands of light and dark bands. The light strips are called I bands and contain only thin filaments. Dark bands are called A-bands and contain thick, thin filaments, with thick filaments encompassing the entire length of the A-band. Thus, the length of the thick filament determines the length of the band A. Goody, R.S. The missing link in the cycle of the transverse muscular bridge. Nature Structural Molecular Biology 10, 773–775 (2003) doi:10.1038/nsb1003-773. Figure 3-10. Sliding filament model of muscle contraction. Muscle contraction occurs by sliding the myofilaments relative to each other into the sarcoma.
A: In relaxed muscles, thin filaments do not completely overlap with thick myosin filaments, and there is a prominent I-band. B: During contraction, a movement of the thin filaments towards the center of the sarcomaer occurs, and as the thin filaments are anchored to the Z disks, their movement leads to a shortening of the sarcomor. The sliding of thin filaments is facilitated by contact with the spherical head domains of myosin-thick bipolar filaments. The sarcolemma has electron-dense spots or rings more or less evenly spaced with large multiunit proteins with cross-membrane membranes. These are analogous to desmosomes, and the proteins they contain are structural proteins that connect the network of cytoskeletal filaments that connect myofibrils to the extracellular matrix. The actin and IF complex of the cytoskeleton and membrane proteins is called costamer. Fig. 3.5 illustrates a sarcoma and highlights the physical orientation of the actin and myosin filaments. The thick filament of myosin contains many heads that, when attached to the thinner actin filaments, form actin-myosin transverse bridges. Essentially, a myosin head resembles a stretched spring that bends when bound to an actin filament and creates a force snap.
The force stroke pushes the actin filament beyond the myosin, resulting in the generation of force and shortening of a single sarcomere (Fig. 3.6). Since the sarcomeres of an entire muscle fiber are connected from one end to the other, their simultaneous contraction shortens the entire muscle. The evolution of contractile muscles has given the higher organisms of the animal kingdom the ability to be mobile in their environment. There are three types of muscles: skeleton, heart and smooth. Myocytes are the cellular unit of muscle structure and contain high concentrations of specialized proteins that use chemical energy to generate mechanical force in the form of cell contraction. Skeletal and cardiac muscles are called striped muscles because of the visible organization of repetitive units of contractile filaments, known as sarcomas, into cylindrical bundles called myofibrils. In mature muscle fibers (striated muscle myocytes), most of the cell volume is occupied by myofibrill, leaving little room for nuclei and the associated Golgi system, mitochondria, sarcoplasmic reticulum (SR; the specialized endoplasmic reticulum of striated muscle), glycogramide granules, and other organelles/structures. In contrast, smooth muscles have large amounts of actin and myosin filaments that are not organized into sarcomeres. Unlike striated muscle cells, which are postmitotic, smooth muscle cells can multiply under physiological and pathological conditions.
The striped muscles are regulated by Ca2+, which is released by the SR and binds to troponin (Tn) on the actin filament. This event releases tropomyosin (Tm) from its position, which blocks the interaction of myosin heads with actin. However, smooth muscle does not contain Tn, and contraction is regulated by the level of phosphorylation of the myosin regulating light chain (RLC). Table 1 summarizes the characteristics of the three different classes of mammalian muscle cells. The two types of striated muscles – skeleton and heart – organize their contractile filaments of actin and myosin into regular arrangements called sarcomeres. These striated muscles are regulated by ca2+, which binds to Tn, releasing Tm to move over the actin and reveal the site of binding to myosin. Smooth muscle also contracts due to the interaction of actin and myosin filaments, but these filaments are not located in regular repetitive networks. Phosphorylation of myosin RLC controls the actin-myosin interaction in smooth muscle. The functional state of the muscle determines the positioning of the transverse bridge and therefore the fine structure of the thick filaments and the entire A-band.
In the relaxed muscle state, which requires the presence of MgATP and very low levels of Ca2+, the myosin heads are found near the surface of the thick filament, which is tightened around the surface of the thick filament tree in a configuration called the super-relaxed state. The two heads of each molecule have slightly different positions and interact specifically with each other (Woodhead et al. 2005). The heads describe a spiral path around the backbone of the thick filament. In skeletal muscle, three parallel helices wrap around the filament. The distance between adjacent planes containing transverse bridges is 14.3 nm and the propeller repeat is ∼43 nm. This helical periodicity is pronounced on the surface of thick filaments of sarcomeres, fixed by rapid freezing, as a result of which the arrangement of the transverse bridge is preserved. This feature is also evident in insulated thick filaments, with contrast enhanced by negative coloration or platinum shading. In electronic microscopic images of thicker sections of relaxed sarcomeres, the A-band shows 11 transverse lines visible at repetition intervals of 43 nm.
These lines are created by the superposition of transverse bridge profiles and accessory proteins C and H (Craig 2004). Myofibrils are made up of thick, thin myofilaments that give the muscle its striped appearance. The thick filaments are made of myosin, and the thin filaments are mainly actin, as well as two other muscle proteins, tropomyosin and troponin. Muscle cells are designed to generate strength and movement. There are three types of mammalian muscles – skeleton, heart and smooth. Skeletal muscles are attached to the bones and move them relative to each other. The heart muscle includes the heart, which pumps blood through the vascular system. .