A non-cross-bridge stiffness in activated frog muscle fibers

Force responses to fast ramp stretches of various amplitude and velocity, applied during tetanic contractions, were measured in single intact fibers from frog tibialis anterior muscle. Experiments were performed at 14 degrees C at approximately 2.1 microm sarcomere length on fibers bathed in Ringer's solution containing various concentrations of 2,3-butanedione monoxime (BDM) to greatly reduce the isometric tension. The fast tension transient produced by the stretch was followed by a period, lasting until relaxation, during which the tension remained constant to a value that greatly exceeded the isometric tension. The excess of tension was termed "static tension," and the ratio between the force and the accompanying sarcomere length change was termed "static stiffness." The static stiffness was independent of the active tension developed by the fiber, and independent of stretch amplitude and stretching velocity in the whole range tested; it increased with sarcomere length in the range 2.1-2.8 microm, to decrease again at longer lengths. Static stiffness increased well ahead of tension during the tetanus rise, and fell ahead of tension during relaxation. These results suggest that activation increased the stiffness of some sarcomeric structure(s) outside the cross-bridges.     

ULTRASTRUCTURE OF THE RESTING AND CONTRACTED STRIATED MUSCLE FIBER AT DIFFERENT DEGREES OF STRETCH

Passive stretch, isometric contraction, and shortening were studied in electron micrographs of striated, non-glycerinated frog muscle fibers. The artifacts due to the different steps of preparation were evaluated by comparing sarcomere length and fiber diameter before, during, and after fixation and after sectioning. Tension and length were recorded in the resting and contracted fiber before and during fixation. The I filaments could be traced to enter the A band between the A filaments on both sides of the I band, creating a zone of overlap which decreased linearly with stretch and increased with shortening. This is consistent with a sliding filament model. The decrease in the length of the A and I filaments during isometric contraction and the finding that fibers stretched to a sarcomere length of 3.7 µ still developed 30 per cent of the maximum tetanic tension could not be explained in terms of the sliding filament model. Shortening of the sarcomeres near the myotendinous junctions which still have overlap could account for only one-sixth of this tension, indicating that even those sarcomeres stretched to such a degree that there is a gap between A and I filaments are activated during isometric contraction (increase in stiffness). Shortening, too, was associated with changes in filament length. The diameter of A filaments remained unaltered with stretch and with isometric contraction. Shortening of 50 per cent was associated with a 13 per cent increase in A filament diameter. The area occupied by the fibrils and by the interfibrillar space increased with shortening, indicating a 20 per cent reduction in the volume of the fibrils when shortening amounted to 40 per cent.     

Kinetics of ATP hydrolysis and tension production in skinned cardiac muscle of the guinea pig

The kinetics of ATP hydrolysis and tension responses were studied simultaneously in a permeabilized preparation of cardiac tissue of the guinea pig. This was achieved by combining laserflash photolysis of P3-1-(2-nitrophenyl)ethyladenosine 5'-triphosphate ("caged-ATP") and a rapid freezing technique. In the presence of calcium ions, tension increased following the photolytic production of ATP with a half-time of 0.3 s. The timecourse of ATP hydrolysis consisted of an initial rapid phase followed by a steady-state hydrolysis rate of 0.4 s-1, indicating that the rate-limiting step of the ATPase in isometric fibers is slower and subsequent to the nucleotide hydrolysis step: the isometric steady state intermediate is probably an actomyosin-ADP complex. In the absence of calcium ions, rigor tension decreased upon the photolytic production of ATP with a half-time of 0.45 s. The time course of ATP hydrolysis was biphasic with a rapid initial phase of ATP hydrolysis, followed by a steady-state hydrolysis rate which was too slow to measure over the time scale of these experiments (less than 0.04 s-1). A comparison of the results obtained in this study with those reported for rabbit skeletal muscle reveals qualitative similarities between cardiac and skeletal muscle and also quantitative differences in their physiological and kinetic behavior.     

Compliance of thin filaments in skinned fibers of rabbit skeletal muscle.

The mechanical compliance (reciprocal of stiffness) of thin filaments was estimated from the relative compliance of single, skinned muscle fibers in rigor at sarcomere lengths between 1.8 and 2.4 micron. The compliance of the fibers was calculated as the ratio of sarcomere length change to tension change during imposition of repetitive cycles of small stretches and releases. Fiber compliance decreased as the sarcomere length was decreased below 2.4 micron. The compliance of the thin filaments could be estimated from this decrement because in this range of lengths overlap between the thick and thin filaments is complete and all of the myosin heads bind to the thin filament in rigor. Thus, the compliance of the overlap region of the sarcomere is constant as length is changed and the decrease in fiber compliance is due to decrease of the nonoverlap length of the thin filaments (the I band). The compliance value obtained for the thin filaments implies that at 2.4-microns sarcomere length, the thin filaments contribute approximately 55% of the total sarcomere compliance. Considering that the sarcomeres are approximately 1.25-fold more compliant in active isometric contractions than in rigor, the thin filaments contribute approximately 44% to sarcomere compliance during isometric contraction.     

X-ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction.

To clarify the extensibility of thin actin and thick myosin filaments in muscle, we examined the spacings of actin and myosin filament-based reflections in x-ray diffraction patterns at high resolution during isometric contraction of frog skeletal muscles and steady lengthening of the active muscles using synchrotron radiation as an intense x-ray source and a storage phosphor plate as a high sensitivity, high resolution area detector. Spacing of the actin meridional reflection at approximately 1/2.7 nm-1, which corresponds to the axial rise per actin subunit in the thin filament, increased about 0.25% during isometric contraction of muscles at full overlap length of thick and thin filaments. The changes in muscles stretched to approximately half overlap of the filaments, when they were scaled linearly up to the full isometric tension, gave an increase of approximately 0.3%. Conversely, the spacing decreased by approximately 0.1% upon activation of muscles at nonoverlap length. Slow stretching of a contracting muscle increased tension and increased this spacing over the isometric contraction value. Scaled up to a 100% tension increase, this corresponds to a approximately 0.26% additional change, consistent with that of the initial isometric contraction. Taken together, the extensibility of the actin filament amounts to 3-4 nm of elongation when a muscle switches from relaxation to maximum isometric contraction. Axial spacings of the layer-line reflections at approximately 1/5.1 nm-1 and approximately 1/5.9 nm-1 corresponding to the pitches of the right- and left-handed genetic helices of the actin filament, showed similar changes to that of the meridional reflection during isometric contraction of muscles at full overlap. The spacing changes of these reflections, which also depend on the mechanical load on the muscle, indicate that elongation is accompanied by slight changes of the actin helical structure possibly because of the axial force exerted by the actomyosin cross-bridges. Additional small spacing changes of the myosin meridional reflections during length changes applied to contracting muscles represented an increase of approximately 0.26% (scaled up to a 100% tension increase) in the myosin periodicity, suggesting that such spacing changes correspond to a tension-related extension of the myosin filaments. Elongation of the myosin filament backbone amounts to approximately 2.1 nm per half sarcomere. The results indicate that a large part (approximately 70%) of the sarcomere compliance of an active muscle is caused by the extensibility of the actin and myosin filaments; 42% of the compliance resides in the actin filaments, and 27% of it is in the myosin filaments.     

Cross-bridge mechanism of residual force enhancement after stretching in a skeletal muscle

A muscle model that uses a modified Langevin equation with actomyosin potentials was used to describe the residual force enhancement after active stretching. Considering that the new model uses cross-bridge theory to describe the residual force enhancement, it is different from other models that use passive stretching elements. Residual force enhancement was simulated using a half sarcomere comprising 100 myosin molecules. In this paper, impulse is defined as the integral of an excess force from the steady isometric force over the time interval for which a stretch is applied. The impulse was calculated from the force response due to fast and slow muscle stretches to demonstrate the viscoelastic property of the cross-bridges. A cross-bridge mechanism was proposed as a way to describe the residual force enhancement on the basis of the impulse results with reference to the compliance of the actin filament. It was assumed that the period of the actin potential increased by 0.5% and the amplitude of the potential decreased by 0.5% when the half sarcomere was stretched by 10%. The residual force enhancement after 21.0% sarcomere stretching was 6.9% of the maximum isometric force of the muscle; this value was due to the increase in the number of cross-bridges.     

Load-dependent regulation of neuromuscular system

Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.     

Lattice swelling with the selective digestion of elastic components in single-skinned fibers of frog muscle.

Changes in the 1.0 lattice spacing during trypsin (0.25 micrograms/ml) treatment in mechanically skinned single fibers of frog muscle was examined by an x-ray diffraction method at various sarcomere lengths. The resting tension of a relaxed fiber was decreased by trypsin treatment but the stiffness of a rigor fiber was not, suggesting that elastic components were selectively digested. With progression of the digestion, the lattice spacing increased remarkably at longer sarcomere lengths and finally became independent of the sarcomere length. The increase in the lattice spacing was proportional to the decrease in the resting tension. These results support our previous suggestion (Higuchi, H., and Y. Umazume, 1986, Biophys. J., 50:385-389) that the lattice spacing decreases at long lengths due to compressive force exerted by a lateral elastic component that connects thick filaments to an axial elastic component. Consequently, it is unlikely that the decrease in the lattice spacing is determined by a decrease in the repulsive force between thick and thin filaments with stretching a fiber.     

The chemo-mechanical coupling relation in the oscillatory contraction-relaxation cycles of insect fibrillar muscle.

The mechanical properties and the activity of the myofibrillar ATPase have been investigated at 21 degrees C on glycerinated back muscle from the water-bug Lethocerus colossicus. When the fibres were held under isometric conditions after stretching them by 0.5--4%, the ATPase required to maintain a given tension increases from 19 to 39 p-moles ATP split for each mg of tension developed as the Ca2+ level is increased from 10(-7) to up to 10(-5) M. The mechanical properties and the ATPase activity have been determined for Ca2+-activated fibres using sinusoidal frequencies of 1--30 HZ and oscillatory amplitudes of 0.5--6% peak-to-peak. In this way the R.M.S. velocity of sinusoidal movement was varied between 0.1-10 mm/sec. The rate of ATP splitting associated with oscillatory tension development, the dynamic tension cost, increases both with Ca2+ and with frequency of oscillation (at 1% peak-to-peak amplitude), becoming as high as four times the isometric value. The oscillatory power output which can be obtained is increased when the Ca2+ level is raised from 10(-7) to 10(-5) M or towards higher amplitudes of oscillation. The chemo-mechanical coupling efficiency increases proportionally with the R.M.S. velocity of muscle movement. In presence of 10(-5) M Ca2+ optimal efficiencies of 5.5--6.2 kcal work per mole ATP split are obtained at R.M.S. velocities of 1.3--2 muscle lengths/sec. The ability of the muscle fibres to perform osciillatory work at the higher frequencies was much reduced at lower Ca2+ levels of 10(-6) or 10(-7) M and the maximal efficiencies never exceeded 2.2 kcal/mole.     

Optical Diffraction Studies of Muscle Fibers

A new technique to monitor light diffraction patterns electrically is applied to frog semitendinosus muscle fibers at various levels of stretch. The intensity of the diffraction lines, sarcomere length change, and the length-dispersion (line width) were calculated by fast analogue circuits and displayed in real time. A heliumneon laser (wavelength 6328 Å) was used as a light source. It was found that the intensity of the first-order diffraction line drops significantly (30-50%) at an optimal sarcomere length of 2.8 μm on isometric tetanic stimulation. Such stimulation produced contraction of half-sarcomeres by about 22 nm presumably by stretching inactive elements such as tendons. The dispersion of the sarcomere lengths is extremely small, and it is proportional to the sarcomere length (less than 4%). The dispersion increases on stimulation. These changes on isometric tetanic stimulation were dependent on sarcomere length. No vibration or oscillation in the averaged length of the sarcomeres was found during isometric tetanus within a resolution of 3 nm; however, our observation of increased length dispersion of the sarcomeres together with detection of the averaged shortening of the sarcomere lengths suggests the presence of asynchronous cyclic motions between thick and thin filaments. An alternative explanation is simply an increase of the length dispersion of sarcomeres without cyclic motions.     

A simple model with myofilament compliance predicts activation-dependent crossbridge kinetics in skinned skeletal fibers

The contribution of thick and thin filaments to skeletal muscle fiber compliance has been shown to be significant. If similar to the compliance of cycling cross-bridges, myofilament compliance could explain the difference in time course of stiffness and force during the rise of tension in a tetanus as well as the difference in Ca(2+) sensitivity of force and stiffness and more rapid phase 2 tension recovery (r) at low Ca(2+) activation. To characterize the contribution of myofilament compliance to sarcomere compliance and isometric force kinetics, the Ca(2+)-activation dependence of sarcomere compliance in single glycerinated rabbit psoas fibers, in the presence of ATP (5.0 mM), was measured using rapid length steps. At steady sarcomere length, the dependence of sarcomere compliance on the level of Ca(2+)-activated force was similar in form to that observed for fibers in rigor where force was varied by changing length. Additionally, the ratio of stiffness/force was elevated at lower force (low [Ca(2+)]) and r was faster, compared with maximum activation. A simple series mechanical model of myofilament and cross-bridge compliance in which only strong cross-bridge binding was activation dependent was used to describe the data. The model fit the data and predicted that the observed activation dependence of r can be explained if myofilament compliance contributes 60-70% of the total fiber compliance, with no requirement that actomyosin kinetics be [Ca(2+)] dependent or that cooperative interactions contribute to strong cross-bridge binding.     

Structural changes of cross-bridges on transition from isometric to shortening state in frog skeletal muscle

Structural changes in the myosin cross-bridges were studied by small-angle x-ray diffraction at a time resolution of 0.53 ms. A frog sartorius muscle, which was electrically stimulated to induce isometric contraction, was released by approximately 1% in 1 ms, and then its length was decreased to allow steady shortening with tension of approximately 30% of the isometric level. Intensity of all reflections reached a constant level in 5-8 ms. Intensity of the 7.2-nm meridional reflection and the (1,0) sampling spot of the 14.5-nm layer line increased after the initial release but returned to the isometric level during steady shortening. The 21.5-nm meridional reflection showed fast and slow components of intensity increase. The intensity of the 10.3-nm layer line, which arises from myosin heads attached to actin, decreased to a steady level in 2 ms, whereas other reflections took longer, 5-20 ms. The results show that myosin heads adapt quickly to an altered level of tension, and that there is a distinct structural state just after a quick release.     

Time-resolved changes in equatorial x-ray diffraction and stiffness during rise of tetanic tension in intact length-clamped single muscle fibers.

We report the first time-resolved x-ray diffraction studies on tetanized intact single muscle fibers of the frog. The 10, 11, 20, 21, 30, and Z equatorial reflections were clearly resolved in the relaxed fiber. The preparation readily withstood 100 1-s duration (0.4-s beam exposure) tetani at 4 degrees C (less than 4% decline of force and no deterioration in the 10, 11 equatorial intensity ratio at rest or during activation). Equatorial intensity changes (10 and 11) and fiber stiffness led tension (t1/2 lead 20 ms at 4 degrees C) during the tetanus rise and lagged during the isometric phase of relaxation. These findings support the existence of a low force cross-bridge state during the rise of tetanic tension and isometric relaxation that is not evident at the tetanus plateau. In "fixed end" tetani lattice expansion occurred with a time course similar to stiffness during the tetanus rise. During relaxation, lattice spacing increased slightly, while the sarcomere length remained isometric, but underwent large changes after the "shoulder" of tension. Under length clamp control, lattice expansion during the tetanus rise was reduced or abolished, and compression (2%) of the lattice was observed. A lattice compression is predicted by certain cross-bridge models of force generation (Schoenberg, M. 1980. Biophys. J. 30:51-68; Schoenberg, M. 1980. Biophys. J. 30:69-78).     

Variations in cross-bridge attachment rate and tension with phosphorylation of myosin in mammalian skinned skeletal muscle fibers. Implications for twitch potentiation in intact muscle

The Ca2+ sensitivities of the rate constant of tension redevelopment (ktr; Brenner, B., and E. Eisenberg. 1986. Proceedings of the National Academy of Sciences. 83:3542-3546) and isometric force during steady-state activation were examined as functions of myosin light chain 2 (LC2) phosphorylation in skinned single fibers from rabbit and rat fast-twitch skeletal muscles. To measure ktr the fiber was activated with Ca2+ and steady isometric tension was allowed to develop; subsequently, the fiber was rapidly (less than 1 ms) released to a shorter length and then reextended by approximately 200 nm per half sarcomere. This maneuver resulted in the complete dissociation of cross-bridges from actin, so that the subsequent redevelopment of tension was related to the rate of cross-bridge reattachment. The time course of tension redevelopment, which was recorded under sarcomere length control, was best fit by a first-order exponential equation (i.e., tension = C(1 - e-kt) to obtain the value of ktr. In control fibers, ktr increased sigmoidally with increases in [Ca2+]; maximum values of ktr were obtained at pCa 4.5 and were significantly greater in rat superficial vastus lateralis fibers (26.1 +/- 1.2 s-1 at 15 degrees C) than in rabbit psoas fibers (18.7 +/- 1.0 s-1). Phosphorylation of LC2 was accomplished by repeated Ca2+ activations (pCa 4.5) of the fibers in solutions containing 6 microM calmodulin and 0.5 microM myosin light chain kinase, a protocol that resulted in an increase in LC2 phosphorylation from approximately 10% in the control fibers to greater than 80% after treatment. After phosphorylation, ktr was unchanged at maximum or very low levels of Ca2+ activation. However, at intermediate levels of Ca2+ activation, between pCa 5.5 and 6.2, there was a significant increase in ktr such that this portion of the ktr-pCa relationship was shifted to the left. The steady-state isometric tension-pCa relationship, which in control fibers was left shifted with respect to the ktr-pCa relationship, was further left-shifted after LC2 phosphorylation. Phosphorylation of LC2 had no effect upon steady-state tension during maximum Ca2+ activation. In fibers from which troponin C was partially extracted to disrupt molecular cooperativity within the thin filament (Moss et al. 1985. Journal of General Physiology. 86:585-600), the effect of LC2 phosphorylation to increase the Ca2+ sensitivity of steady-state isometric force was no longer evident, although the effect of phosphorylation to increase ktr was unaffected by this maneuver.(ABSTRACT TRUNCATED AT 400 WORDS)     

The dependence of isometric tension, isometric ATPase activity, and shortening velocity of limulus muscle on the MgATP concentration.

The dependence of the isometric tension, the velocity of unloaded shortening, and the steady-state rate of MgATP hydrolysis on the MgATP concentration (range 0.01-5 mM MgATP) was studied in Ca-activated skinned Limulus muscle fibers. With increasing MgATP concentration the isometric tension increased to a peak at approximately 0.1 mM, and slightly decreased in the range up to 5 mM MgATP. The velocity of unloaded shortening depended on the MgATP concentration roughly according to the Michaelis-Menten law of saturation kinetics with a Michaelis-Menten constant Kv = 95 microM and a maximum shortening velocity of 0.07 muscle lengths s-1; the detachment rate of the cross-bridges during unloaded shortening was 24 s-1. The rate of MgATP splitting also depended hyperbolically on the MgATP concentration with a Michaelis-Menten constant Ka = 129 microM and a maximum turnover frequency of 0.5-1 s-1. The results are discussed in terms of a cross-bridge model based on a biochemical scheme of ATP hydrolysis by actin and myosin in solution.     

Study of the mechanics and small-angle equatorial x-ray pattern of the frog skeletal muscle during transition and rigor at different temperatures

Mechanical characteristics and low-angle equatorial X-ray patterns from frog sartorius muscle passing into iodoacetate rigor under isometric conditions at temperatures 2 degrees-25 degrees C were studied. It is ascertained that during the rigor tension development at all the temperatures Z-reflection intensity increases and those of the (10), (11), (20), (21) and (30) reflections decrease. The last three reflections disappear then still in the phase of the rigor tension development. It is found that the sarcomere lengths remain not always invariable, especially at high temperatures, when the muscle passes into rigor, and can both decrease and increase in the sample place which is investigated by means of X-ray diffraction method. It is shown that the decrease of the I10/I11 relation in some experiments at high temperatures is only due to the sarcomere length decrease. The merging time of the Z and (11) reflections depends both on the temperature and on the sarcomere length change. Thus essential changes correlated with the rigor tension development, and resulted in the Z-reflection intensity increase take place in tetragonal lattice of Z-band and in the I-band region located near Z-band. In A-band the hexagonal lattice order change for the worse is marked only. It is proposed that the mechanism of the rigor tension development differs from that of tension development in ordinary contraction of the skeletal muscle.     

Acceleration of the ATPase activity of glycerol-treated muscle fibers by repeated stretch-release cycles.

Glycerol-treated muscle fiber bundles were fixed at their rest length in 50 mM KC1, 2 mM MgC1(2), and 10 micron CaC1(2) at pH 7.8 and 0 degrees C in the presence of sufficient amounts of ATP, creatine kinase, and creatine phosphate. The fiber bundles were stretched linearly with time for 0.3 s at a constant amplitude, suddenly released, then fixed at the rest length for a constant time interval (alpha seconds). The stretch-release cycle was repeated, and the ATPase activity (the rate of ADP liberation) [EC 3.6.1.3] was measured. It was found that: 1. ATPase was activated by repeated stretch-release. As repetitive stretch-release of 1--2% of the rest length caused maximum activation, we usually selected a value of 2.5% of the rest length. The activation of ATPase was found to be a function of the duration, alpha, of the isometric phase after sudden release from stretching. The ATPase activity of fiber bundles was almost unaffected when they were oscillated by a simple stretch-release without an isometric phase after the sudden release (alpha=0). 2. The ATPase activity of oscillated muscle fibers increased with increase in the value of alpha, reached a maximal level, then decreased gradually with further increase of alpha to a value slightly larger than that of static fibers. At 0 degrees C, the value of alpha for the maximum activation was observed at about 2 s, and the maximum activity was about 2.5 times that of static fibers. At 20 degrees C, the alpha value for maximum activation was about 0.5 s, and the maximum activity was about 1.8 times that of static fibers. 3. The time course of ADP liberation after one stretch-release cycle could be easily calculated from the ATPase activity of the summed durations of the isometric phase, alpha, assuming that the ATPase activation was turned off and on by the stretching and release, respectively, and that the state of cross-bridges immediately after the stretch-release was independent of alpha of the cycle. The rate of ADP liberation after stretch-release thus obtained showed a short lag phase, a sigmoidal increase, a decrease to almost zero, then a return to nearly the original level (the rate of static fibers). About 1.3 mol of ATP per mol of myosin was hydrolyzed at both 0 degrees C and 20 degrees C during one cycle of the changes in the rate of ADP liberation.     

The sarcomere length-tension relation in skeletal muscle

Tension development during isometric tetani in single fibers of frog semitendinosus muscle occurs in three phases: (a) in initial fast-rise phase; (b) a slow-rise phase; and (c) a plateau, which lasts greater than 10 s. The slow-rise phase has previously been assumed to rise out of a progressive increase of sarcomere length dispersion along the fiber (Gordon et al. 1966. J. Physiol. [Lond.]. 184:143--169;184:170-- 192). Consequently, the "true" tetanic tension has been considered to be the one existing before the onset of the slow-rise phase; this is obtained by extrapolating the slowly rising tension back to the start of the tetanus. In the study by Gordon et al. (1966. J. Physiol. [Lond.] 184:170--192), as well as in the present study, the relation between this extrapolated tension and sarcomere length gave the familiar linear descending limb of the length-tension relation. We tested the assumption that the slow rise of tension was due to a progressive increase in sarcomere length dispersion. During the fast rise, the slow rise, and the plateau of tension, the sarcomere length dispersion at any area along the muscle was less than 4% of the average sarcomere length. Therefore, a progressive increase of sarcomere length dispersion during contraction appears unable to account for the slow rise of tetanic tension. A sarcomere length-tension relation was constructed from the levels of tension and sarcomere length measured during the plateau. Tension was independent of sarcomere length between 1.9 and 2.6 microgram, and declined to 50% maximal at 3.4 microgram. This result is difficult to reconcile with the cross-bridge model of force generation.     

Force enhancement above the initial isometric force on the descending limb of the force-length relationship

Edman et al. (J. General Physiol. 80 (1982) 769) observed in single fibres of frog that the steady-state forces following active fibre stretch were greater than the purely isometric force obtained at the length from which the stretch was initiated. Operating on the descending limb of the force-length relationship, such a result can only be explained within the framework of the sarcomere length non-uniformity theory, if some fibre segments shortened during the fibre stretch. However, such a result was not found, leaving Edman's observation unexplained. Force enhancement above the initial isometric force has not been investigated systematically in whole muscle, and therefore it is not known whether this property is also part of whole muscle mechanics. The purpose of this study was to test if the steady-state forces following active stretch of cat semitendinosus were greater than the corresponding purely isometric forces at the muscle length from which the stretch was started. Cat semitendinosus was stretched by various amounts on the descending limb of the force-length relationship, and the steady-state forces following these stretches were compared to the corresponding isometric forces at the initial and final muscle lengths. In 109 of 131 tests, the steady-state forces following stretching were greater than the isometric forces at the initial muscle lengths. Force enhancement increased with increasing amounts of stretching, and force enhancement above the initial isometric force was more likely to occur following stretches of great compared to small amplitude. Passive forces following active muscle stretching were often significantly greater than the passive forces at the same muscle length following an isometric contraction or a passive stretching of the muscle. This observation was made consistently at the longest muscle lengths tested. It appears, therefore, that there is a passive force that accounts for part of the force enhancement above the isometric force at the initial muscle length, and that provides increased passive force when a muscle is actively, rather than passively, stretched at long muscle lengths. We conclude that cat semitendinosus demonstrates steady-state force enhancement above the corresponding purely isometric force at the initial muscle length on the descending limb of the force-length relationship for many contractile conditions, and that a unique, and so far undetected, passive, parallel element contributes to this force enhancement, particularly at long muscle lengths where muscle is assumed to be most vulnerable to injuries associated with sarcomere length instability.