The Physiologic Basis of Muscle Contraction - Essay Example

Sliding Filament Theory: The Physiologic Basis of Muscle Contraction Skeletal muscles are attached to the bones of the skeleton. They serveto produce movements and are used in locomotion, maintenance of posture, and almost in any activities a body performs. Microscopically, their cells are elongated and multinuclear, and the contractile elements within them show cross-striations. Each skeletal muscle is made up of a large number of skeletal muscle fibers, which are long thin cylindrical cells that contain many nuclei. Individual muscle fibers are enclosed by connective tissue sheaths called the endomysium, and groups of muscle fibers are invested by connective tissue sheath called the erimysium to form bundles which are known as muscle fascicles. Surrounding the whole muscle is a layer of connective tissue, epimysium that encloses the individual fascicules together. The individual muscle fibers are made up of filamentous bundles that run along the length of the fiber. Most of the interior of the fibre consists of the protein filaments which constitute the contractile apparatus, grouped together in bundles called myofibrils. Each myofibril consists of a repeating unit, known as a sarcomere. The alignment of the sarcomeres between adjacent muscle fibers is responsible for the characteristic striations in the striated skeletal muscle fibers. The sarcomere is the fundamental contractile unit of the skeletal muscles. When a muscle fiber is viewed by polarized light, the sarcomeres are seen as alternating dark and light zones. Some regions appear dark because they refract the polarized light. This property is called anisotropy, and the corresponding band is known as an A band. The light regions do not refract polarized light and are called isotropic and are denoted as I bands. Each I band is divided by a characteristic line known as a Z line, and the unit between successive Z lines is the sarcomere [1]. Under electron microscopic examination with high magnification, the A bands are seen to be composed of thick filaments arranged in a regular order. The I bands consist of thin filaments. When the muscle is in the resting state, that is, when there is no shortening of the fibers due to contraction, a pale area can be seen in the center of the A band. This is known as the H zone, and it corresponds to the region where the thick and thin filaments do not overlap, which otherwise is the case throughout the muscle fiber architecture. In the center of each H zone, there is a line called M line. It is in this line, links are formed between adjacent thick filaments. The principal protein of the A bands is myosin, while that of I bands is actin. The interaction between these proteins is fundamental to the contractile process in the skeletal muscle at the ultrastructural and molecular levels. There are two types of actin filaments. One is globular in shape, known as globular or G actin subunits, and the other is filamentous of F actin. The actin filaments of the I band are made by joining many G actin subunits together by polymerization to form F actin. The F actin, in turn, is stabilized by binding to the Z line. The thick filaments are made up of an assembly of myosin molecules together. Each myosin molecule consists of two heavy chains. Each of these heavy chains has two light chains associated with a head region that is globular. The junction between the head region and the long tail contains a hinge. This hinge allows the myosin to generate the force required for muscle contraction. The tail regions of the myosin molecules associate together to form the thick filaments. Each thick filament consists of several hundred myosin molecules [2]. The sliding filament theory explains muscle contraction, and the structure of skeletal muscle provides important clues to the mechanism of contraction. The width of the A bands or thick filament areas in striated muscle remains constant, regardless of the length of the entire muscle fiber, while the width of the I bands or the thin-filament areas varies directly with the length of the fiber. At the edges of the A band are fainter bands whose width also varies. These represent material extending into the A band from the I bands. The spacing between Z lines also depends directly on the length of the fiber. The lengths of the thin and thick myofilaments remain constant despite changes in fiber length. The sliding filament theory proposes that changes in overall fiber length are directly associated with changes in the overlap between the two sets of filaments. This signifies that the thin filaments telescope into the array of thick filaments, leading to a interdigitation during contraction. This interdigitation accounts for the change in the length of the muscle fiber. It is accomplished by the interaction of the globular heads of the myosin molecules. This creates crossbridges that project from the thick filaments [3]. The crossbridges are the sites where force and shortening are produced and where the chemical energy stored in the muscle is transformed into mechanical energy. The total shortening of each sarcomere is only about 1m, but a muscle fiber contains thousands of such sarcomeres placed end to end. Therefore, when an action potential is generated in a muscle, this arrangement in effect multiplies all the small sarcomere length changes, resulting into a large overall shortening of the muscle. Similarly, the amount of force exerted by a single sarcomere is small; again, there are several thousands of sarcomeres arranged side by side, resulting in the production of considerable force. The structure of the muscle fibers facilitates this process. In muscles, narrow tubules run from the sarcolemma transversely across the fiber at the junction of the A and I bands. These are known as T tubules. Each myofibril is surrounded by the sarcoplasmic reticulum. Where the T tubules and the sarcoplasmic reticulum come into contact, the sarcoplasmic reticulum is enlarged to form the terminal cisternae. Each T tubule is in close contact with the cisternae of two regions of sarcoplasmic reticulum and the whole complex is called a triad. This triad has an important role in initiation of muscle contraction following a nerve stimulus, and this phenomenon is known as excitation-contraction coupling [4]. To elaborate further, skeletal muscle, like nerve, is an excitable tissue, and stimulation of a muscle fiber at one point will rapidly lead to excitation of the whole cell. The neural stimulus leads to generation of end plate potential, and this depolarizes the muscle fiber membrane in the region adjacent to the end-plate. This is the triggering event in that initiates an action potential that would propagate away from the end plate along the whole length of the muscle fiber. The passage of the muscle action potential is followed by contraction of the muscle fiber and the development of tension. The process by which a muscle action potential triggers a contraction is known as excitation-contraction coupling. To answer the question, how does a muscle action potential leads to the contractile response, it can be stated that calcium ions are the main initiators of the process at the biochemical levels. It has been found that significant amounts of Ca2+ are stored in the sarcoplasmic reticulum, and a considerable proportion of that is released during contraction. It is now thought convincingly that the depolarization of the plasma membrane during the muscle action potential spreads along the T tubules, and there it causes Ca2+ channels in the sarcoplasmic reticulum to open. As a result, Ca2+ stored in the sarcoplasmic reticulum is released and the level of Ca2+ in the sarcoplasm rises. This rise in Ca2+ triggers the contraction of the muscle fiber. If solutions of actin and myosin are mixed in vitro, a great increase in viscosity occurs, due to the formation of a complex called actomyosin. Actomyosin is an ATPase, which is activated by magnesium ions. A mixture of purified actin and purified myosin will split ATP in the absence of calcium ions. However 'natural' actomyosin can only split ATP if there is a low concentration of calcium ions present. In the absence of calcium ions, addition of ATP to a solution of natural actomyosin results in a decrease in viscosity, suggesting that the actin-myosin complex becomes dissociated. These observations can be used to make plausible suggestions about the mechanism of actin and myosin interaction within the filamentous array of the living muscle. In the resting condition, there is an adequate concentration of ATP and a very low concentration of calcium ions, so there are no interaction between the actin and myosin and no ATP splitting. On activation, the calcium ion concentration rises, leading to formation of cross-bridges between the two sets of filaments, and ATP is split and sliding occurs [5]. As discussed earlier, the individual myosin molecules of the thick filaments have two globular heads and a long thin tail region. They are arranged in such a way that the thin tail regions associate together to form the backbone of the thick filaments while the thicker head regions project outwards to form cross-bridges with the neighboring thin filaments. The actin molecules link together to form a long polymer chain, Actin F. Each actin molecule in the chain is able to bind one myosin head region. Actin and myosin molecules dissociate when a molecule of ATP is bound by the myosin. The breakdown of ATP and the subsequent release of inorganic phosphate cause a change in the angle of the head region of the myosin molecule, enabling it to move relative to the thin filament. Once again, ATP causes the dissociation between the actin and myosin and the cycle is repeated. This process is known as cross-bridge cycling and results in the thick and thin filaments sliding past each other, thus shortening the fiber. This process is not synchronized across the myofibril, thus while some myosin head groups are dissociating from the actin, others are binding or developing their power stroke. This results in a uniform contractile train along the muscle fiber. In the absence of ATP, the actin filament is bound to the S1 heads but there is no movement. On adding ATP the actin moves across, like a caterpillar across a lawn, at a speed comparable with the sliding of filaments in whole muscle. Cross-bridge action is thus a cyclical process. Each cross-bridge will attach to the adjacent actin filament, its lever arm will swing so as to pull the actin and myosin filaments past each other, then it will detach from the actin filament. The cross-bridge is then ready to attach to a new site on the actin filament and so repeat the cycle. The energy for each turn of the cycle is provided by the breakdown of one molecule of ATP to ADP and inorganic phosphate [6]. The sliding-filament theory of muscle contraction provides a clear explanation for the length-tension relationship of skeletal muscle. When the muscle is at its natural resting length, the thin and thick filaments overlap optimally and form the maximum number of cross-bridges. When the muscle is stretched, the degree of overlap between the thin and thick filaments is reduced, and the number of cross-bridges falls. This leads to a decline in the ability of the muscle to generate tension. When the muscle is shorter than its natural resting length, the thin filaments already fully overlap the thick filaments, but the filaments from each end of the sarcomere touch in the center of the A band and each interferes with the motion of the other. As a result, tension development declines. When the thin and thick filaments fully overlap, the A bands encroach and abut the Z lines and tension development is no longer possible [7]. To sum up, according to the sliding theory, sliding of the filaments of actin and myosin between themselves is the basis of muscle contraction. The cycle of events consists of a repetitive process of contraction that involves a cyclic interaction between the thick and thin filaments. The steps that comprise the crossbridge cycle are attachment of thick-filament crossbridges to sites along the thin filaments, production of a mechanical movement, crossbridge detachment from the thin filaments, and subsequent reattachment of the crossbridges at different sites along the thin filaments. These mechanical changes are closely related to the biochemistry of the contractile proteins. In fact, the crossbridge association between actin and myosin actually functions as an enzyme, actomyosin ATPase that catalyzes the breakdown of ATP and releases its stored chemical energy [8]. Most of our knowledge of this process comes from studies on skeletal muscle, but the same basic steps are followed in all muscle types. Reference List 1. Junquiera, L.C. and Carneiro, J. Basic histology, (10th edition), Chapter 10. McGraw-Hill, New York., 2003. 2. Aidley, D.J. The physiology of excitable cells (4th edn), Chapters 18 and 21. Cambridge University Press, Cambridge, 1998. 3. Bagshaw, C. R.. Muscle Contraction, 2nd edn. London: Chapman & Hall, 1993. 4. Jones, D.A., Round, J.M., and de Haan, A.. Skeletal muscle from molecules to movement. Churchill-Livingstone, Edinburgh, 2004. 5. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. Molecular biology of the cell (4th edn), pp. 949-968. Garland, New York, 2002. 6. Buller, A. J. The Contractile Behaviour of Mammalian Skeletal Muscle (Oxford Biology Reader No. 36) London: Oxford University Press, 1975. 7. Huxley, H. E.. The structural basis of contraction and regulation in skeletal muscle. In Molecular Basis of Motility, ed. L. M. G. Heilmeyer Jr, J. C. Ruegg & Th. Wieland. Berlin: Springer-Verlag, 1976. 8. Huxley, H. E.. Sliding filaments and molecular motile systems. J. Biol. Chem. 1990. 265, 8347-50. Read More