Fig. ME1. Changes in sarcomere length and in I band length during contraction of an electrically stimulated frog fiber. (From A.F. Huxley and Niedergerke, 1954).
Mechanism of Skeletal Muscle Contraction
The sliding filament theory: It is well accepted that this is the basic mechanism for muscle contraction. Two groups in England, A.F. Huxley and Niedergerke (1954), and H.E. Huxley and Hanson (1954) are the founders of the theory. Their classical experiments are shown in Figures ME1 and ME 2:
Fig. ME1 shows a living frog muscle fiber under the interference microscope. A bands appear dark, I bands are light. The length of the sarcomeres, A and I bands were measured on densitometer tracings. The fiber was stimulated electrically and it was allowed to shorten. On the left side for each frame two numbers are given. The upper numbers indicate the sarcomere length, which in successive times during contraction decreased from 3.10 to 2.93 to 2.70 to 2.37m . The lower numbers indicate A band length, 1.43, 1.45, 1.50, and 1.48 m , that means, it was unchanged during contraction.
Fig. ME2 shows the pictures of glycerol extracted psoas fibrils under phase contrast microscope. A bands are dark, I bands are light, in the middle of I bands the Z lines are seen. Four sarcomeres of one fibril are pictured during ATP induced contraction. A bands did not change in length, but the I bands shortened, in the last frame the I bands disappeared.
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Fig. ME1. Changes in sarcomere length and in I band length during contraction of an electrically stimulated frog fiber. (From A.F. Huxley and Niedergerke, 1954). |
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Fig. ME2. Changes in sarcomere length and in I band length during contraction of a glycerol-extracted fibril contracted by ATP. (From H.E. Huxley and Hanson, 1954). |
Further experimentation revealed that during contraction the length of the actin containing thin filaments and the length of the myosin containing thick filaments remain constant. Thus, during contraction the length of the sarcomere and I band decrease, the overlap between thick and thin filaments increases, the length of the thick and thin filaments remains unchanged. Consequently, the filaments must slide past each other.
Length-tension relationship: The physiological interpretation of the sliding filament theory was tested by measuring the tension of a single muscle fiber at different sarcomere length (Gordon et al., 1966). Figure ME3 illustrates the experiment. Maximum tension was obtained at rest length, between 2.0-2.25 m , when all crossbridges were in the overlap region between thick and thin filaments. When the muscle fiber was stretched so that the sarcomere length increased from 2.25 to 3.675 m and consequently the number of crossbridges in the overlap region decreased from maximum to zero, the tension fell from 100% to 0.
The crossbridges are uniformly distributed along the thick filaments with the exception of a short bare zone in the middle. The crossbridges seem to be identical and are the site of the interaction between thick and thin filaments. The tension is the algebraic sum of the tension produced at each individual site. At or above rest length the tension is directly proportional to the number of crossbridges in the overlap region between thick and thin filaments.
Below rest length, when the thin filaments meet in the center of A band or they start to interact with the oppositely directed crossbridge sites past the bare zone (in the middle of the sarcomere), tension drops off.
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Fig. ME3. Length-tension relationship of a single frog semitendinosus muscle fiber. (From Gordon et al., 1966). The numbers 1 through 6 on the length tension curve correspond to the numbers on the schematic diagram of thick and thin filament arrangement. In this way the relationship between thick and thin filaments can be compared to the tension at various sarcomere length.
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With a new ATP a new cycle may begin and the cycling may continue till the regulatory mechanism stops the interaction of actin and myosin. As shown in Fig. ME4, ATP is needed for step 1 that is for the detachment of myosin from actin. In case of ATP depletion, the cycle is arrested. When actin and myosin are permanently bound in the absence of ATP, the muscle becomes rigid. This state is called rigor mortis.
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Fig. ME4. Crossbridge cycle and its relation to actomyosin ATPase. (Courtesy of Dr. Jack Rall). |
Summary of Events in Skeletal Muscle Contraction
Excitation
The sarcolemma is depolarized and the action potential propagates
The action potential spreads inside along the T-tubules
The signal is transmitted from T-tubule to terminal sacs of sarcoplasmic reticulum
Calcium is released from sarcoplasmic reticulum into sarcoplasm
Contraction
Calcium binds to troponin
Cooperative conformational changes take place in troponin-tropomyosin system
The inhibition of actin and myosin interaction is released
Crossbridges of myosin filaments are attached to actin filaments
Tension is exerted, and/or the muscle shortens by the sliding filament mechanism
Relaxation
Calcium is pumped into sarcoplasmic reticulum
Crossbridges are detached from the thin filaments
Troponin-tropomyosin regulated inhibition of actin and myosin interaction is restored
Active tension disappears and the rest length is restored
References
Gordon, A.M., Huxley, A.F., and Julian, F.J. (1966). The variation in isometric tension with sarcomere length in vertebrate muscle fibres. J. Physiol., 184, 170-192.
Huxley, A.F. and Niedergerke, R. (1954). Structural changes in muscle during contraction. Interference microscopy of living muscle fibres. Nature, 173, 971-973.
Huxley, H.E. and Hanson, J. (1954). Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation. Nature, 173, 973-976.
