scholarly journals The effects of inorganic phosphate on muscle force development and energetics: challenges in modelling related to experimental uncertainties

Author(s):  
Alf Månsson

Abstract Muscle force and power are developed by myosin cross-bridges, which cyclically attach to actin, undergo a force-generating transition and detach under turnover of ATP. The force-generating transition is intimately associated with release of inorganic phosphate (Pi) but the exact sequence of events in relation to the actual Pi release step is controversial. Details of this process are reflected in the relationships between [Pi] and the developed force and shortening velocity. In order to account for these relationships, models have proposed branched kinetic pathways or loose coupling between biochemical and force-generating transitions. A key hypothesis underlying the present study is that such complexities are not required to explain changes in the force–velocity relationship and ATP turnover rate with altered [Pi]. We therefore set out to test if models without branched kinetic paths and Pi-release occurring before the main force-generating transition can account for effects of varied [Pi] (0.1–25 mM). The models tested, one assuming either linear or non-linear cross-bridge elasticity, account well for critical aspects of muscle contraction at 0.5 mM Pi but their capacity to account for the maximum power output vary. We find that the models, within experimental uncertainties, account for the relationship between [Pi] and isometric force as well as between [Pi] and the velocity of shortening at low loads. However, in apparent contradiction with available experimental findings, the tested models produce an anomalous force–velocity relationship at elevated [Pi] and high loads with more than one possible velocity for a given load. Nevertheless, considering experimental uncertainties and effects of sarcomere non-uniformities, these discrepancies are insufficient to refute the tested models in favour of more complex alternatives.

2007 ◽  
Vol 102 (6) ◽  
pp. 2294-2300 ◽  
Author(s):  
A. N. Devrome ◽  
B. R. MacIntosh

Edman has reported that the force-velocity relationship (FVR) departs from Hill's classic hyperbola near 0.80 of measured isometric force ( J Physiol 404: 301–321, 1988). The purpose of this study was to investigate the biphasic nature of the FVR in the rested state and after some recovery from fatigue in the rat medial gastrocnemius muscle in situ. Force-velocity characteristics were determined before and during recovery from fatigue induced by intermittent stimulation at 170 Hz for 100 ms each second for 6 min. Force-velocity data were obtained for isotonic contractions with 100 ms of 200-Hz stimulation, including several measurements with loads above 0.80 of measured isometric force. The force-velocity data obtained in this study were fit well by a double-hyperbolic equation. A departure from Hill's classic hyperbola was found at 0.88 ± 0.01 of measured isometric force, which is higher than the ∼0.80 reported by Edman et al. for isolated frog fibers. After 45 min of recovery, maximum shortening velocity was 86 ± 2% of prefatigue, but neither curvature nor predicted isometric force was significantly different from prefatigue. The location of the departure from Hill's classic hyperbola was not different after this recovery from the fatiguing contractions. Including an isometric point in the data set will not yield the same values for maximal velocity and the degree of curvature as would be obtained using the double hyperbola approach. Data up to 0.88 of measured isometric force can be used to fit data to the Hill equation.


2017 ◽  
Vol 38 (10) ◽  
pp. 741-746 ◽  
Author(s):  
Vladimir Grbic ◽  
Sasa Djuric ◽  
Olivera Knezevic ◽  
Dragan Mirkov ◽  
Aleksandar Nedeljkovic ◽  
...  

AbstractSingle outcomes of standard isokinetic dynamometry tests do not discern between various muscle mechanical capacities. In this study, we aimed to (1) evaluate the shape and strength of the force-velocity relationship of knee extensors, as observed in isokinetic tests conducted at a wide range of angular velocities, and (2) explore the concurrent validity of a simple 2-velocity method. Thirteen physically active females were tested for both the peak and averaged knee extensor concentric force exerted at the angular velocities of 30°–240°/s recorded in the 90°–170° range of knee extension. The results revealed strong (0.960<R<0.998) linear force-velocity relationships that depict the maximum muscle force (i.e. the force-intercept), velocity (velocity-intercept), and power (their product). Moreover, the line drawn through only the 60° and 180°/s data (the ‘2-velocity method’) revealed a high level of agreement with the force-velocity relationship obtained (0.76<R<0.97; all power<0.001); while the force-intercept highly correlated (0.68<R<0.84; all power≤0.01) with the directly measured isometric force. The 2-velocity method could therefore be developed into a standard method for isokinetic testing of mechanical capacities of knee extensors and, if supported by further research, other muscles. This brief and fatigue-free testing procedure could discern between muscle force, velocity, and power-producing capacities.


2008 ◽  
Vol 294 (1) ◽  
pp. R200-R210 ◽  
Author(s):  
Annette M. Gabaldón ◽  
Frank E. Nelson ◽  
Thomas J. Roberts

The force-velocity properties of skeletal muscle have an important influence on locomotor performance. All skeletal muscles produce less force the faster they shorten and typically develop maximal power at velocities of ∼30% of maximum shortening velocity (Vmax). We used direct measurements of muscle mechanical function in two ankle extensor muscles of wild turkeys to test the hypothesis that during level running muscles operate at velocities that favor force rather than power. Sonomicrometer measurements of muscle length, tendon strain-gauge measurements of muscle force, and bipolar electromyographs were taken as animals ran over a range of speeds and inclines. These measurements were integrated with previously measured values of muscle Vmax for these muscles to calculate relative shortening velocity (V/Vmax). At all speeds for level running the V/Vmax values of the lateral gastrocnemius and the peroneus longus were low (<0.05), corresponding to the region of the force-velocity relationship where the muscles were capable of producing 90% of peak isometric force but only 35% of peak isotonic power. V/Vmax increased in response to the demand for mechanical power with increases in running incline and decreased to negative values to absorb energy during downhill running. Measurements of integrated electromyograph activity indicated that the volume of muscle required to produce a given force increased from level to uphill running. This observation is consistent with the idea that V/Vmax is an important determinant of locomotor cost because it affects the volume of muscle that must be recruited to support body weight.


1996 ◽  
Vol 270 (2) ◽  
pp. E203-E208
Author(s):  
A. L. Ruzycky ◽  
B. T. Ameredes

The relationship between cross-bridge cycling rate and isometric stress was investigated in rat myometrium. Stress production by myometrial strips was measured under resting, K+ depolarization, and oxytocin-stimulated conditions. Cross-bridge cycling rates were determined from measurements of maximal unloaded shortening velocity, using the quick-release method. Force redevelopment after the quick release was used as an index of cross-bridge attachment. With maximal K+ stimulation, stress increased with increased cross-bridge cycling (+76%; P < 0.05) and attached cross bridges (+112%; P < 0.05). Addition of oxytocin during K+ stimulation further increased stress (+30%; P < 0.05). With this force component, the cross-bridge cycling rate decreased (-60%; P < 0.05) similar to that under resting conditions. Attached cross-bridges did not increase with this additional stress. The results suggest two distinct mechanisms mediating myometrial contractions. One requires elevated intracellular calcium and rapidly cycling cross bridges. The other mechanism may be independent of calcium and appears to be mediated by slowly cycling cross bridges, supporting greater unit stress.


1996 ◽  
Vol 271 (2) ◽  
pp. C676-C683 ◽  
Author(s):  
J. J. Widrick ◽  
S. W. Trappe ◽  
D. L. Costill ◽  
R. H. Fitts

Gastrocnemius muscle fiber bundles were obtained by needle biopsy from five middle-aged sedentary men (SED group) and six age-matched endurance-trained master runners (RUN group). A single chemically permeabilized fiber segment was mounted between a force transducer and a position motor, subjected to a series of isotonic contractions at maximal Ca2+ activation (15 degrees C), and subsequently run on a 5% polyacrylamide gel to determine myosin heavy chain composition. The Hill equation was fit to the data obtained for each individual fiber (r2 > or = 0.98). For the SED group, fiber force-velocity parameters varied (P < 0.05) with fiber myosin heavy chain expression as follows: peak force, no differences: peak tension (force/fiber cross-sectional area), type IIx > type IIa > type I; maximal shortening velocity (Vmax, defined as y-intercept of force-velocity relationship), type IIx = type IIa > type I; a/Pzero (where a is a constant with dimensions of force and Pzero is peak isometric force), type IIx > type IIa > type I. Consequently, type IIx fibers produced twice as much peak power as type IIa fibers, whereas type IIa fibers produced about five times more peak power than type I fibers. RUN type I and IIa fibers were smaller in diameter and produced less peak force than SED type I and IIa fibers. The absolute peak power output of RUN type I and IIa fibers was 13 and 27% less, respectively, than peak power of similarly typed SED fibers. However, type I and IIa Vmax and a/Pzero were not different between the SED and RUN groups, and RUN type I and IIa power deficits disappeared after power was normalized for differences in fiber diameter. Thus the reduced absolute peak power output of the type I and IIa fibers from the master runners was a result of the smaller diameter of these fibers and a corresponding reduction in their peak isometric force production. This impairment in absolute peak power production at the single fiber level may be in part responsible for the reduced in vivo power output previously observed for endurance-trained athletes.


1990 ◽  
Vol 259 (4) ◽  
pp. H1118-H1125 ◽  
Author(s):  
J. S. Herland ◽  
F. J. Julian ◽  
D. G. Stephenson

The slack test method has been adapted for measurement of unloaded velocity of shortening in rat ventricular trabeculae that were skinned with saponin (50 micrograms/ml for 30 min). The method was sensitive enough to detect a 17% reversible change in the unloaded velocity of shortening produced by a 3 degrees C change in temperature. At pCa 5.30 (80-90% activation), halothane, enflurane, and isoflurane each slowed the shortening velocity by 25-30% at dose levels of 8 mM or greater but not at 4 mM or less. At pCa 5.48 (50-60% activation), halothane slowed the shortening velocity by 20-45% at dose levels of 4 mM or greater but not at 2 mM. The slowing effect of anesthetics on shortening velocity showed saturation at 8 mM for halothane, enflurane, and isoflurane when activation was at pCa 5.30. Saturation occurred at 4 mM for halothane when the pCa was 5.48. This result indicates that the dose-response relationship may be narrow, such that it can be demonstrated between 2 and 4 mM halothane for pCa 5.48 and between 4 and 8 mM halothane for pCa 5.30. The anesthetic dose dependence of isometric force and length axis intercept did not generally follow the same relationship as for the shortening velocity. Thus in several instances force did not significantly decrease when the velocity of shortening did. This may be interpreted as lack of simple inhibition by anesthetics on the number of interacting cross-bridges and as direct influence by anesthetics on the cross-bridge cycle.


2000 ◽  
Vol 89 (6) ◽  
pp. 2215-2219 ◽  
Author(s):  
Bill T. Ameredes ◽  
Wen-Zhi Zhan ◽  
Y. S. Prakash ◽  
Rene Vandenboom ◽  
Gary C. Sieck

We hypothesized that decrements in maximum power output (W˙max) of the rat diaphragm (Dia) muscle with repetitive activation are due to a disproportionate reduction in force (force fatigue) compared with a slowing of shortening velocity (velocity fatigue). Segments of midcostal Dia muscle were mounted in vitro (26°C) and stimulated directly at 75 Hz in 400-ms-duration trains repeated each second (duty cycle = 0.4) for 120 s. A novel technique was used to monitor instantaneous reductions in maximum specific force (Po) andW˙max during fatigue. During each stimulus train, activation was isometric for the initial 360 ms during which Po was measured; the muscle was then allowed to shorten at a constant velocity (30% V max) for the final 40 ms, and W˙max was determined. Compared with initial values, after 120 s of repetitive activation, Po andW˙max decreased by 75 and 73%, respectively. Maximum shortening velocity was measured in two ways: by extrapolation of the force-velocity relationship ( V max) and using the slack test [maximum unloaded shortening velocity ( V o)]. After 120 s of repetitive activation, V max slowed by 44%, whereas V o slowed by 22%. Thus the decrease inW˙max with repetitive activation was dominated by force fatigue, with velocity fatigue playing a secondary role. On the basis of a greater slowing of V max vs. V o, we also conclude that force and power fatigue cannot be attributed simply to the total inactivation of the most fatigable fiber types.


1982 ◽  
Vol 52 (4) ◽  
pp. 930-938 ◽  
Author(s):  
Y. Kikuchi ◽  
H. Sasaki ◽  
K. Sekizawa ◽  
K. Aihara ◽  
T. Takishima

We examined the force-velocity relationship of the respiratory muscles in normal subjects under nearly isotonic conditions, taking into consideration the pleural pressure (Ppl) changes during maximum forced expirations (MFE). We used an electromagnetic valve (EMV) to select the Ppl value at the onset of mouth flow; and both a pressure reservoir and a variable resistance to control the Ppl changes after the opening of the EMV during MFE. To simulate isotonic conditions and to obtain the shortening velocity of the contractile element (CE), we mathematically corrected the velocity of the series elastic component (SEC), using a modified version of Hill's equation. Although the maximum tension at total lung capacity (TLC) [1,156 +/- 215 (SD) g/cm] was larger than that at functional residual capacity (FRC) (782 +/- 97 g/cm) there was no significant difference in the maximum shortening velocity, 3.4 +/- 1.0 and 3.2 +/- 0.8 circumference/s at TLC and FRC, respectively. The mean values of k (slope) for the SEC at TLC and FRC were 19 +/- 4 and 18 +/- 5 circumference-1, respectively, and they were not significantly different. We concluded that the force-velocity relationship of the expiratory muscles exhibited the same mechanical properties as that of the other skeletal muscles.


Medicina ◽  
2020 ◽  
Vol 56 (5) ◽  
pp. 249
Author(s):  
Hans Degens ◽  
David A. Jones

Background and Objectives: Muscle fatigue is characterised by (1) loss of force, (2) decreased maximal shortening velocity and (3) a greater resistance to stretch that could be due to reduced intracellular Ca2+ and increased Pi, which alter cross bridge kinetics. Materials and Methods: To investigate this, we used (1) 2,3-butanedione monoxime (BDM), believed to increase the proportion of attached but non-force-generating cross bridges; (2) Pi that increases the proportion of attached cross bridges, but with Pi still attached; and (3) reduced activating Ca2+. We used permeabilised rat soleus fibres, activated with pCa 4.5 at 15 °C. Results: The addition of 1 mM BDM or 15 mM Pi, or the lowering of the Ca2+ to pCa 5.5, all reduced the isometric force by around 50%. Stiffness decreased in proportion to isometric force when the fibres were activated at pCa 5.5, but was well maintained in the presence of Pi and BDM. Force enhancement after a stretch increased with the length of stretch and Pi, suggesting a role for titin. Maximum shortening velocity was reduced by about 50% in the presence of BDM and pCa 5.5, but was slightly increased by Pi. Neither decreasing Ca2+ nor increasing Pi alone mimicked the effects of fatigue on muscle contractile characteristics entirely. Only BDM elicited a decrease of force and slowing with maintained stiffness, similar to the situation in fatigued muscle. Conclusions: This suggests that in fatigue, there is an accumulation of attached but low-force cross bridges that cannot be the result of the combined action of reduced Ca2+ or increased Pi alone, but is probably due to a combination of factors that change during fatigue.


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