Thin myofilaments

Structure of / -actin from a nonmuscle cell. As described in the text, a-and /i-actins are very similar. The shape is like a rectangular pillow, with dimensions of roughly 5.5 x 5.5 x 3.5 nm, with a cleft in it. The U-shape formed by this arrangement of the four major domains is stabilized by the binding of Mg-ATP in the cleft, as shown. In the absence of bound nucleotide, actin monomers denature readily. [From Molecular Cell Biology, 3rd ed., by Lodish et al. (Eds). W.H. Freeman, New York, 

G-actin is very highly conserved, both across actin genes within a species and across species. Apparently, the need for so many functional binding sites in a molecule of that size leaves few options for nonlethal mutations. Among the actins sequenced from 30 widely divergent species, there were only 32 amino acid substitutions. One implication of this is that when differences in contractile properties are observed between various types of muscle, those differences must be due to the motor protein (myosin) or to the various regulatory proteins. 

Model of a thin filament. Two tropomyosin filaments, each composed of two subfilaments, wind around the actin chain. They block the binding of the globular heads of myosin molecules (in thick filaments) to the actin molecules. Troponin consists of three polypeptides and binds to both actin and tropomyosin. 

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Fig. 2.7. Cortical muscle element consisting of a contractile myofibril portion and a mycyton portion. Arrows indicate two of the thick myofilaments distributed among the more numerous thin myofilaments. (After Lumsden Hildreth, 1983.)...

Muscle fibers contain long cylindrical myofibrils (typically 1-2 /xm in diameter) aligned longitudinally and consisting of interpenetrating arrays of thin myofilaments (6-7 nm in diameter) and thick filaments (15-16 nm in diameter). These structures are the contractile apparatus of the fiber (Figure 21-3). 

Muscle force generation is believed to arise from the formation of crossbridge bonds between thick and thin myofilaments within the basic building block of muscle, the sarcomere. These structures, in the nanometer to micrometer range, must be viewed by electron microscopy or x-ray diffraction, limiting study to fixed, dead material. Consequently, muscle contraction at the sarcomere level must be described by models that integrate metabolic and structural information. 

Muscle proteins proteins present in muscle and constituting 20 % of muscle tissue. The insoluble contractile proteins are organized in myofibrils which consist of organized arrays of thick and thin myofilaments Thick filaments (about 1.5 im long, 12-16 nm diam.) contain 200-400 molecules of the protein myosin (Fig.l). 

As mentioned above, the junctional SR is connected to sheets of perpendicular SR (Fig. 4), which extend from the PM through a peripheral cytoplasmic region with lower myofilament density into the myoplasm. It is proposed that during the active state of wave-like [Ca2+]j oscillations, Ca2+ taken up by the junctional SR is released by these perpendicular sheets near the calmodulin, which is tethered to the myosin light chain kinase (MLCK) of the thin filaments (M. Walsh, personal communication, 2001). This process would enhance the specificity and efficiency of Ca2+ regulation of contraction. 

The muscle is a highly organized tissue, built up of individual cells known as fibres, which are held together by connective tissue. Each muscle fibre consists of a high number of single strands of myofibrils. The myofibrils are again comprised of myofilaments. The myofilaments are divided into thin and thick filaments, which mainly contain two filamentary proteins, actin and myosin, respectively. The myofibrils occupy approximately 80% of the muscle cell volume, and the majority of the water, which makes up about 75% of the muscle, is located in the spaces between thin and thick filaments. A schematic drawing of muscle structure is shown in Fig. 1. 

Figure 13.5 Electron micrograph of part of a longitudinal section of a myofibril. Identification of components and the mechanism of contraction. When a muscle fibre is stimulated to contract, the actin and myosin filaments react by sliding past each other but with no change in length of either myofilament. The thick myosin strands in the A band are relatively stationary, whereas the thin actin filaments, which are attached to the Z discs, extend further into the A band and may eventually obliterate the H band. Because the thin filaments are attached to Z discs, the discs are drawn toward each other, so that the sarcomeres, the distance between the adjacent Z-discs, are compressed, the myofibril is shortened, and contraction of the muscle occurs. Contraction, therefore, is not due to a shortening of either the actin or the myosin filaments but is due to an increase in the overlap between the filaments. The force is generated by millions of cross-bridges interacting with actin filaments (Fig. 13.6). The electron micrograph was kindly provided by Professor D.S. Smith.

April, E. W., Brandt, P. W., and Elliott, G. F. (1971). The myofilament lattice Studies on isolated fibers. I. The constancy of the unit-cell volume with variation in sarcomere length in a lattice in which the thin-to-thick myofilament ratio is 6 1./. Cell Biol. 51, 72-82. 

The muscle cell membrane is termed the plasma-lemma. The cytoplasm of the muscle cell is filled with myofilaments, which form the myofibrils. Myofibrils are composed of sarcomeres, which consist of longitudinally directed thin and thick filaments and perpendicularly disposed z bands that are a-actin filaments. The myofibrils form the contractile apparatus of the muscle. 

Each myofibril consists of two different protein structures myofilaments. These are myosin thick (15 nm x 1.5 pm) and thin (7 nm x 1 pm) filaments made from actin, tropomyosin, and troponin. 

Calcium accumulation and overload secondary to ischemia impair ventricular relaxation as well as contraction. This is apparently a result of impaired calcium uptake after systole from the myofilaments, leading to a less negative decline in the pressure in the ventricle over time. Impaired relaxation is associated with enhanced diastolic stiffness, decreased rate of wall thinning, and slowed pressure decay, producing an upward shift in the ventricular pressure-volume relationship put more simply, MVO2 is likely to be increased secondary to increased wall tension. Impairment of both diastolic and systolic function leads to elevation of the filling pressure of the left ventricle. 

Small JV, Herzog M, Barth M, Draeger A (1990) Supercontracted state of vertebrate smooth muscle cell fragments reveals myofilament lengths. J Cell Biol 111 24512461 Smith CW, Pritchard K, Marston SB (1987) The mechanism of Ca regulation of vascular smooth muscle thin filaments by caldesmon and calmodulin. J Biol Chem 262 116122... 

Asynchrony in bond formation and unequal numbers of bonds formed in each half sarcomere, as well as mechanical disturbances such as shortening and imposed length transients, cause movement of thick with respect to thin filaments. Since myofilament masses are taken into account these movements take the form of damped vibrations. Such vibrations occur with a spectrum of frequencies due to the distributed system properties. 

For the thick filaments the number of filaments is half of the number of the thin filaments but the radius is twice as large. Therefore both arms of the viscous drag couple will exert the same force on the two sets of the inter-digitated myofilaments and cause them to slide into each other. 

In a muscle tissue (Fig lb), the fiber cells are thin and elongated as opposed to the polygonal cells in plants. The major myofibrillar proteins, myosin and actin, form the myofilament bundles in the sarcoplasm of the fiber cell. Bundles of fiber cells form the muscle tissue. Connective tissue distributed between individual (endomysium) and bundles of fiber cells (perimysium) as well as around the whole muscle (epimysium) holds the cells and the muscle tissue together. Majority of lipids is located in the adipose tissue depots associated with the connective tissue between the bundles of fiber cells in poultry and red meat as well as fish muscle [2]. 

In principle, microfibrils are composed by two types of myofilaments, i.e. the thick myosin filament, (j) = 100 A and L = 1.5 pm, and the thin actin filaments, ( ) = 50 A and L = 2.0 pm respectively. In cross section, under very high magnification, both A and I bands can be seen to be hexagonal networks. Figure 4.3. These networks are apparently ordered and fixed at the M- and Z-lines. In the region where the A and I bands overlap (sometimes known as the H band) the two hexagonal networks intermesh so that each myosin filament is surrounded by six actin filaments. These networks appear to be anchored to (and through) the cell membrane in two ways. At the ends of fibrils, special structures... 

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