Molecular Basis For Muscular Contraction
Suggested Reading: Guyton Chapter 6
Muscle Fiber: All skeletal muscles are made of numerous fibers. Each of these fibers in turn is made up of successively smaller subunits. In most muscles the fibers extend the entire length of the muscle...except for about 2 percent of the fibers. Each is innervated by only one verve ending, located near the middle of the fiber. Guyton, page 73
Myofibrils: Make up the muscle fiber. Made up by myosin filaments and actin filaments. Guyton, page 73
Myofilaments: Made up of multiple myosin molecules. They for a myosin filament. These are the "thick" filaments. The heads will attach to the actin filaments to shorten the muscle fiber. Guyton, page 76
Actin: The "thin" filament. Composed of three protein components: actin, tropomyosin, and troponin. Guyton, page 77
Tropomyosin: One of the molecules on the actin filament. They are connected loosely with the F-actin strands, wrapped spirally around the sides of the F-actin helix. In the resting state, the tropomyosin molecules are believed to lie on top of the active sites of the actin strands, so that attraction cannot occur between the actin and myosin filaments to cause contraction. Each tropomyosin molecule covers about seven of these active sites. Guyton, page 77
Troponin (3): Attached near one end of each tropomyosin molecule is still another protein molecule called troponin. This is actually a complex of three loosely bound protein subunits, each of which plays a specific role in the control of muscle contraction. One of the subunits (troponin I) has a strong affinity for actin, another (troponin T) for tropomyosin, and a third (troponin C) for calcium ions. This complex is believed to attach the tropomyosin to the actin. The strong affinity of troponin for calcium ions is believed to initiate the contraction process. Guyton, page 77
Light/Heavy Meromyosin: 2 heavy chains wrap spirally around each other to forma double helix. One end of each of these chains is folded into a globular polypeptide structure called the myosin head. Thus, there are two free heads lying side by side at one end of the double helix myosin molecule; the elongated portion of the coiled helix is called the tail. The 4 light chains are also parts of the myosin heads, two to each head. These light chains help control the function of the head during muscle contraction. Guyton, page 76-77
Cross Bridges: The protruding arms and heads together. Each cross-bridge is believed to be flexible at two points called hinges, one where the arm leaves the body of the myosin filament and the other where the two heads attach to the arm. Guyton, page 77
Sliding Filament Mechanism: Demonstrates the basic mechanism of muscle contraction. In the relaxed state, the ends of the actin filaments derived from two successive Z discs barely begin to overlap one another, while at the same time lying adjacent to the myosin filaments. On the other hand, in the contracted state, these actin filaments have been pulled inward among the myosin filaments, so that the now overlap one another to a major extent. Also, the Z discs have been pulled by the actin filaments up to the ends of the myosin filaments. Indeed, during intense contraction, the actin filaments can be pulled together so tightly that the ends of the myosin filaments buckle. Guyton, page 76
Sarcomere: The portion of a myofibril (or of the whole muscle fiber) that lies between two successive Z discs. Guyton, page 74
Sarcoplasmic Reticulum: An extensive endoplasmic reticulum, in the muscle fiber. They hold about 10,000 X’s more calcium than the intracellular fluid.
Transverse Tubules: They are very small and run transverse to the myofibrils. They begin at the cell membrane and penetrate all the way from one side of the muscle fiber t the opposite side. They are full of Extra-Cellular-Fluid.
Terminal Cisternae: Part of the sarcoplasmic reticulum that are "bulbulous" and reach out and probably touch the T-tubules. Carries the voltage from the action potential into the sarcoplasmic reticulum. They hold the high concentration of Calcium ions. Guyton, page 92
Identify the basic structural components of a single skeletal muscle fiber, fibril, and filament: The sarcolema is the cell membrane of the muscle fiber. Within the sarcolema are actin and myosin filaments called myofibrils. Each muscle fiber contains several hundred to several thousand myofibrils. Each myofibril has laying side by side about 1500 myosin filaments and 3000 actin filaments, these filaments are responsible for muscle contraction. (see page 74)
Define what is meant by the term "sarcomere" and name the structures present in each of the various "bands" seen with light and electron microscopy: A sarcomere is the portion of a myofibril that lies between 2 successive Z discs. When looking at a muscle under microscopy various bands can be seen. The light bands contain only actin filaments and are called I bands because they are isotropic to polarized light. The dark bands contain the myosin filaments as well as the ends of the actin filaments where they overlap the myosin and are called A bands because they are anisotropic to polarized light.
Name and describe the various subcomponents of the thick and thin filaments, their molecular characteristics, and their structural arrangement: The myosin filament is composed of multiple myosin molecules. The myosin molecule is composed of six polypeptide chains, two heavy chains and four light chains. The two heavy chains wrap spirally around each other to form a double helix. One end of these chains is folded into a globular polypeptide structure called the myosin head. Thus there are two free heads lying side by side at one end of the double helix myosin molecule; the elongated portion of the double helix is called the tail. The four light chains are also parts of the myosin heads, two to each head. These light chains help control the function of the head during muscle contraction. The myosin filament is made up of 200 or more individual myosin molecules. The tails of the myosin molecules bundle together to form the body of the filament while many heads of the molecules hang outward to the sides of the body. Part of the helix portion of each myosin molecule extends to the side along with the head, thus providing an arm that extends the head outward from the body. The protruding arms and heads together are called cross bridges. Each cross bridge is believed to be flexible at two points called hinges. figure 6-5,pp76) The myosin filament itself is twisted so that each successive set of cross bridges is axially displaced from the previous set by 120 degrees. This ensures that the cross bridges extend in all directions around the filament. Another feature of the myosin head that is essential for muscle contraction is that it functions as an ATPase enzyme.
The actin filament is also complex. It is composed of three protein components: actin, tropomyosin, and troponin. A detailed description of the actin filament can be found on pp77.
Describe the general concepts involved in the "sliding filament" theory of muscle contraction: Demonstrates the basic mechanism of muscle contraction. In the relaxed state, the ends of the actin filaments derived from two successive Z discs barely begin to overlap one another, while at the same time lying adjacent to the myosin filaments. On the other hand, in the contracted state, these actin filaments have been pulled inward among the myosin filaments, so that the now overlap one another to a major extent. Also, the Z discs have been pulled by the actin filaments up to the ends of the myosin filaments. Indeed, during intense contraction, the actin filaments can be pulled together so tightly that the ends of the myosin filaments buckle. Guyton, page 76
Discuss the proposed molecular mechanisms by which actin and myosin filaments interact to cause shortening of the sarcomere: It is believed that the active sites on the normal actin filament of the relaxed muscle are inhibited or physically covered by the troponin-tropomyosin complex. Consequently, the sites cannot attach to the heads of thee myosin filaments to cause contraction. Before contraction can take place, the inhibitory effect of the troponin-tropomyosin complex must itself be inhibited. This brings us to the role of the calcium ions. In the presence of large amounts of calcium ions, the inhibitory effect of the troponin-tropomyosin on the actin filaments is itself inhibited. The mechanism of this is not known, but one suggestion is the following: When calcium ions combine with troponin C, each molecule of which can bind strongly with up to four calcium ions, the troponin complex supposedly undergoes a conformational change that in some way tugs on the tropomyosin molecule and supposedly moves it deeper into the groove between the two actin strands. This "uncovers" the active sites of the actin, thus allowing contraction to proceed.
As soon as the actin filament becomes activated by the calcium ions, the heads of the cross-bridges from the myosin filaments become attracted to the active sites of the actin filament, and this, in some way, causes contraction to occur.
Describe the characteristics and probable mechanisms involved in the relationship between the degree of overlap of the actin and myosin filaments and the forces developed by individual sarcomeres and intact muscles: There is maximum contraction when there is maximum overlap between the actin filaments and the cross-bridges of the myosin filaments, and it supports the idea that the greater the number of cross-bridges pulling the actin filaments, the greater the strength of contraction. Guyton, page 79
Identify and quantify the sources and utilization of energy
by a muscle fiber:
1): At rest: ????
2): During contraction: W = L X D Muscle contraction depends on energy supplied by ATP. Most of this energy is required to actuate the walk-along mechanism by which the cross-bridges pull the actin filaments. Guyton, page 80
3): During relaxation: ????
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