scholarly journals The O2 cost of the tension-time integral in isolated single myocytes during fatigue

2010 ◽  
Vol 298 (4) ◽  
pp. R983-R988 ◽  
Author(s):  
Russell T. Hepple ◽  
Richard A. Howlett ◽  
Casey A. Kindig ◽  
Creed M. Stary ◽  
Michael C. Hogan

One proposed explanation for the V̇o2 slow component is that lower-threshold motor units may fatigue and develop little or no tension but continue to use O2, thereby resulting in a dissociation of cellular respiration from force generation. The present study used intact isolated single myocytes with differing fatigue resistance profiles to investigate the relationship between fatigue, tension development, and aerobic metabolism. Single Xenopus skeletal muscle myofibers were allocated to a fast-fatiguing (FF) or a slow-fatiguing (SF) group, based on the contraction frequency required to elicit a fall in tension to 60% of peak. Phosphorescence quenching of a porphyrin compound was used to determine Δ intracellular Po2 (PiO2; a proxy for V̇o2), and developed isometric tension was monitored to allow calculation of the time-integrated tension (TxT). Although peak ΔPiO2 was not different between groups ( P = 0.36), peak tension was lower ( P < 0.05) in SF vs. FF (1.97 ± 0. 17 V vs. 2. 73 ± 0.30 V, respectively) and time to 60% of peak tension was significantly longer in SF vs. FF (242 ± 10 s vs. 203 ± 10 s, respectively). Before fatigue, both ΔPiO2 and TxT rose proportionally with contraction frequency in SF and FF, resulting in ΔPiO2/TxT being identical between groups. At fatigue, TxT fell dramatically in both groups, but ΔPiO2 decreased proportionately only in the FF group, resulting in an increase in ΔPiO2/TxT in the SF group relative to the prefatigue condition. These data show that more fatigue-resistant fibers maintain aerobic metabolism as they fatigue, resulting in an increased O2 cost of contractions that could contribute to the V̇o2 slow component seen in whole body exercise.

1986 ◽  
Vol 56 (2) ◽  
pp. 494-506 ◽  
Author(s):  
B. R. Botterman ◽  
G. A. Iwamoto ◽  
W. J. Gonyea

Single motor units of the flexor carpi radialis (FCR) muscle were activated with a series of constant-rate stimulus trains to study the relation between the frequency of activation and isometric tension development (F-T relation). The tension produced by each stimulus train was expressed as a percentage of the maximum tension-time area (Amax) found for a given unit. Between 25 and 75% Amax a clear separation was seen in the rates needed to produce the same relative tension for the F-T curves of slow-twitch (type S) and fast-twitch (type F) units. Over the steepest portion of the F-T curve (25-50% Amax), where tension output was most sensitive to changes in activation rate, type F units required substantially higher stimulation rates (30 pps) to achieve the same relative tension output as type S units. Furthermore, the frequency range that corresponded to the steep portion of the curve was 2.3 times greater for type F units. For both type S and F units, twitch duration was deemed to be an important determinant of the F-T curve, as has been shown previously. A direct continuous relation was seen between the integrated twitch time (ITT) and the stimulus interval needed to produce 50% Amax (r = 0.94, P less than 0.001). Thus, units that had relatively brief twitches required higher activation rates to achieve the same relative percentage of Amax. Comparison of F-T curves from FCR with those derived by other investigators for cat hindlimb units (medial gastrocnemius and peroneus longus) revealed that significant differences in activation rates were needed to produce the same percentage of Amax throughout the midrange of the F-T curve. At 50% Amax, type F units in FCR required activation rates approximately 20 pps higher than type F units in the hindlimb. Type S units in FCR required only slightly higher rates (approximately equal to 5 pps). Based on a number of well-founded assumptions, F-T curves derived from FCR units were used to estimate the potential contribution of rate coding to total muscle tension by type S and F units. This analysis leads to the conclusion that rate modulation is a potentially important factor in the gradation of tension for the FCR muscle.


2014 ◽  
Vol 307 (3) ◽  
pp. H353-H360 ◽  
Author(s):  
Jared R. Tangney ◽  
Stuart G. Campbell ◽  
Andrew D. McCulloch ◽  
Jeffrey H. Omens

Dyssynchronous activation of the heart leads to abnormal regional systolic stretch. In vivo studies have suggested that the timing of systolic stretch can affect regional tension and external work development. In the present study, we measured the direct effects of systolic stretch timing on the magnitude of tension and external work development in isolated murine right ventricular papillary muscles. A servomotor was used to impose precisely timed stretches relative to electrical activation while a force transducer measured force output and strain was monitored using a charge-couple device camera and topical markers. Stretches taking place during peak intracellular Ca2+ statistically increased peak tension up to 270%, whereas external work due to stretches in this interval reached values of 500 J/m. An experimental analysis showed that time-varying elastance overestimated peak tension by 100% for stretches occurring after peak isometric tension. The addition of the force-velocity relation explained some effects of stretches occurring before the peak of the Ca2+ transient but had no effect in later stretches. An estimate of transient deactivation was measured by performing quick stretches to dissociate cross-bridges. The timing of transient deactivation explained the remaining differences between the model and experiment. These results suggest that stretch near the start of cardiac tension development substantially increases twitch tension and mechanical work production, whereas late stretches decrease external work. While the increased work can mostly be explained by the time-varying elastance of cardiac muscle, the decreased work in muscles stretched after the peak of the Ca2+ transient is largely due to myofilament deactivation.


1967 ◽  
Vol 50 (3) ◽  
pp. 661-676 ◽  
Author(s):  
Edmund H. Sonnenblick

The course of active state in heart muscle has been analyzed using a modified quick release method. The onset of maximum active state was found to be delayed, requiring 110–500 msec from time of stimulation, while the time to peak isometric tension required 250–650 msec. Further, the time from stimulation to peak tension was linearly related to the time required to establish maximum intensity of active state as well as to the duration of maximum active state. The duration of maximum active state was prolonged (90–220 msec), occupying most of the latter half of the rising phase of the isometric contraction. Norepinephrine (10-5 M) shortened the latency from electrical stimulus to mechanical response, accelerated the onset of maximum active state, increased its intensity, decreased its duration, and accelerated its rate of decline. These changes were accompanied by an increase in the rate of tension development and the tension developed while the time from stimulation to peak isometric tension was abbreviated. Similar findings were shown for strophanthidin (1 µg/ml) although lesser decrements in the duration of maximum active state and time to peak tension were found than with norepinephrine for similar increments in the maximum intensity of active state.


2005 ◽  
Vol 98 (5) ◽  
pp. 1639-1645 ◽  
Author(s):  
Casey A. Kindig ◽  
Richard A. Howlett ◽  
Michael C. Hogan

It has been suggested that skeletal muscle O2 uptake (V̇o2) kinetics follow a first-order control model. Consistent with that, V̇o2 should show both 1) similar onset kinetics and 2) an on-off symmetry across submaximal work intensities regardless of the metabolic perturbation. To date, consensus on this issue has not been reached in whole body studies due to numerous confounding factors associated with O2 availability and fiber-type recruitment. To test whether single myocytes demonstrate similar intracellular Po2 (PiO2) on- and off-transient kinetics at varying work intensities, we studied Xenopus laevis single myocyte ( n = 8) PiO2 via phosphorescence quenching during two bouts of electrically induced isometric muscle contractions of 200 (low)- and 400 (high)-ms contraction duration (1 contraction every 4 s, 15 min between trials, order randomized). The fall in PiO2, which is inversely proportional to the net increase in V̇o2, was significantly greater ( P < 0.05) during the high (24.1 ± 3.2 Torr) vs. low (17.4 ± 1.6 Torr) contraction bout. However, the mean response time (MRT; time to 63% of the overall change) for the fall in PiO2 from resting baseline to end contractions was not different (high, 77.8 ± 11.5 vs. low, 76.1 ± 13.6 s; P > 0.05) between trials. The initial rate of change at contraction onset, defined as ΔPiO2/MRT, was significantly greater ( P < 0.05) in high compared with low. PiO2 off-transient MRT from the end of the contraction bout to initial baseline was unchanged (high, 83.3 ± 18.3 vs. low, 80.4 ± 21.6 s; P > 0.05) between high and low trials. These data revealed that PiO2 dynamics in frog isolated skeletal myocytes were invariant despite differing contraction durations and, by inference, metabolic demands. Thus these findings demonstrate that mitochondria can respond more rapidly at the initial onset of contractions when challenged with an augmented metabolic stimulus in accordance with an apparent first-order rate law.


1988 ◽  
Vol 59 (5) ◽  
pp. 1510-1523 ◽  
Author(s):  
G. Horcholle-Bossavit ◽  
L. Jami ◽  
J. Petit ◽  
R. Vejsada ◽  
D. Zytnicki

1. The discharges from individual Golgi tendon organs of peroneus tertius and brevis muscles were recorded in anesthetized cats. Responses to unfused isometric contractions of single motor units and combinations of motor units were compared with responses to contractions eliciting muscle shortening (i.e., shortening contractions). 2. In 75% of the examined instances, the effect of muscle shortening during unfused contractions was a slight decrease in tendon organ activation, in keeping with the reduction of contractile tension recorded at the muscle tendon. In other instances there was either no change in tendon organ response or, in less than 10% of instances, a slight increase For two motor units eliciting similar activation of a given tendon organ under isometric conditions, the effect of shortening contraction was not necessarily the same. 3. The reductions observed in tendon organ discharges upon muscle shortening were less than proportional to the reductions of contractile tension and difficult to correlate with the properties of motor units, as determined under isometric conditions. The present observations suggest three main reasons for this lack of relation. 4. The first reason depended on the properties of motor units, in that the relation between length changes and tension changes was not the same for all units. Two motor units developing similar isometric tensions did not necessarily produce the same degree of muscle shortening. Some units produced relatively significant shortening without much loss of tension. 5. Second, the dynamic sensitivity of tendon organs is known to exert a major influence on their responses to isometric unfused contractions, accounting for 1:1 driving of discharge during tension oscillations and high frequency bursts upon abrupt increase of tension. Although less tension was produced and the rate of tension development was slower in shortening contractions, similar manifestations of the dynamic sensitivity of tendon organs were observed. In such cases, the responses of tendon organs were the same whether or not the muscle shortened during contraction. 6. Third, when several motor units were stimulated in combination, the unloading influences of in-parallel units were facilitated by muscle shortening so that unloading effects, which were hardly visible under isometric conditions became evident during shortening contractions.


1994 ◽  
Vol 266 (1) ◽  
pp. H68-H78 ◽  
Author(s):  
C. R. Cory ◽  
R. W. Grange ◽  
M. E. Houston

The loss of load-sensitive relaxation observed in the pressure-overloaded heart may reflect a strategy of slowed cytosolic Ca2+ uptake to yield a prolongation of the active state of the muscle and a decrease in cellular energy expenditure. A decrease in the potential of the sarcoplasmic reticulum (SR) to resequester cytosolic Ca2+ during diastole could contribute to this attenuated load sensitivity. To test this hypothesis, both in vitro mechanical function of anterior papillary muscles and the SR Ca2+ sequestration potential of female guinea pig left ventricle were compared in cardiac hypertrophy (Hyp) and sham-operated (Sham) groups. Twenty-one days of pressure overload induced by coarctation of the suprarenal, subdiaphragmatic aorta resulted in a 36% increase in left ventricular mass in the Hyp. Peak isometric tension, the rate of isometric tension development, and the maximal rates of isometric and isotonic relaxation were significantly reduced in Hyp. Load-sensitive relaxation were significantly reduced in Hyp. Load-sensitive relaxation quantified by the ratio of a rapid loading to unloading force step in isotonically contracting papillary muscle was reduced 50% in Hyp muscles. Maximum activity of SR Ca(2+)-adenosinetriphosphatase (ATPase) measured under optimal conditions (37 degrees C; saturating Ca2+) was unaltered, but at low free Ca2+ concentrations (0.65 microM), it was decreased by 43% of the Sham response. Bivariate regression analysis revealed a significant (r = 0.84; P = 0.009) relationship between the decrease in SR Ca(2+)-ATPase activity and the loss of load-sensitive relaxation after aortic coarctation. Stimulation of the SR Ca(2+)-ATPase by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase resulted in a 2.6-fold increase for Sham but only a 1.6-fold increase for Hyp. Semiquantitative Western blot radioimmunoassays revealed that the changes in SR Ca(2+)-ATPase activity were not due to decreases in the content of the Ca(2+)-ATPase protein or phospholamban. Our data directly implicate a role for decreased SR function in attenuated load sensitivity. A purposeful downregulation of SR Ca2+ uptake likely results from a qualitative rather than a quantitative change in the ATPase and possibly one of its key regulators, phospholamban.


2013 ◽  
Vol 109 (11) ◽  
pp. 2705-2711 ◽  
Author(s):  
M. Bączyk ◽  
A. Hałuszka ◽  
W. Mrówczyński ◽  
J. Celichowski ◽  
P. Krutki

The study aimed at determining the influence of a whole body vibration (WBV) on electrophysiological properties of spinal motoneurons. The WBV training was performed on adult male Wistar rats, 5 days a week, for 5 wk, and each daily session consisted of four 30-s runs of vibration at 50 Hz. Motoneuron properties were investigated intracellularly during experiments on deeply anesthetized animals. The experimental group subjected to the WBV consisted of seven rats, and the control group of nine rats. The WBV treatment induced no significant changes in the passive membrane properties of motoneurons. However, the WBV-evoked adaptations in excitability and firing properties were observed, and they were limited to fast-type motoneurons. A significant decrease in rheobase current and a decrease in the minimum and the maximum currents required to evoke steady-state firing in motoneurons were revealed. These changes resulted in a leftward shift of the frequency-current relationship, combined with an increase in slope of this curve. The functional relevance of the described adaptive changes is the ability of fast motoneurons of rats subjected to the WBV to produce series of action potentials at higher frequencies in a response to the same intensity of activation. Previous studies proved that WBV induces changes in the contractile parameters predominantly of fast motor units (MUs). The data obtained in our experiment shed a new light to possible explanation of these results, suggesting that neuronal factors also play a substantial role in MU adaptation.


2007 ◽  
Vol 293 (1) ◽  
pp. R392-R401 ◽  
Author(s):  
Andrew M. Jones ◽  
Daryl P. Wilkerson ◽  
Nicolas J. Berger ◽  
Jonathan Fulford

We hypothesized that a period of endurance training would result in a speeding of muscle phosphocreatine concentration ([PCr]) kinetics over the fundamental phase of the response and a reduction in the amplitude of the [PCr] slow component during high-intensity exercise. Six male subjects (age 26 ± 5 yr) completed 5 wk of single-legged knee-extension exercise training with the alternate leg serving as a control. Before and after the intervention period, the subjects completed incremental and high-intensity step exercise tests of 6-min duration with both legs separately inside the bore of a whole-body magnetic resonance spectrometer. The time-to-exhaustion during incremental exercise was not changed in the control leg [preintervention group (PRE): 19.4 ± 2.3 min vs. postintervention group (POST): 19.4 ± 1.9 min] but was significantly increased in the trained leg (PRE: 19.6 ± 1.6 min vs. POST: 22.0 ± 2.2 min; P < 0.05). During step exercise, there were no significant changes in the control leg, but end-exercise pH and [PCr] were higher after vs. before training. The time constant for the [PCr] kinetics over the fundamental exponential region of the response was not significantly altered in either the control leg (PRE: 40 ± 13 s vs. POST: 43 ± 10 s) or the trained leg (PRE: 38 ± 8 s vs. POST: 40 ± 12 s). However, the amplitude of the [PCr] slow component was significantly reduced in the trained leg (PRE: 15 ± 7 vs. POST: 7 ± 7% change in [PCr]; P < 0.05) with there being no change in the control leg (PRE: 13 ± 8 vs. POST: 12 ± 10% change in [PCr]). The attenuation of the [PCr] slow component might be mechanistically linked with enhanced exercise tolerance following endurance training.


2020 ◽  
Author(s):  
Riemer JK Vegter ◽  
Sebastiaan van den Brink ◽  
Leonora J Mouton ◽  
Anita Sibeijn-Kuiper ◽  
Lucas H.V. van der Woude ◽  
...  

Abstract Background: Evaluation of the effect of human upper body training regimens may benefit from knowledge of local energy expenditure in arm muscles. To that end, we developed a novel asynchronous arm-crank ergometry platform for use in a clinical magnetic resonance (MR) scanner with 31P spectroscopy capability to study arm muscle energetics. The utility of the platform was tested in an investigation of the impact of daily practice on the energetic efficiency of execution of an arm-cranking task (ACT) in healthy subjects. Results: We recorded the first ever in vivo 31P MR spectra from the human biceps bracii muscle during ACT execution pre- and post-three weeks of daily practice bouts, respectively. Complementary datasets on whole body oxygen consumption, arm muscle electrical activity, arm-force and power output, respectively, were obtained in the mock-up scanner. The mean gross mechanical efficiency of execution of the ACT significantly increased 1.5-fold from 5.7 ± 1.2% to 8.6 ± 1.7% (P<0.05) after training, respectively. However, in only one subject this improvement was associated with recruitment of strictly oxidative motor units in the working biceps muscle. In all other subjects, biceps pH fell below 6.8 during exercise indicating recruitment of anaerobic motor units, the magnitude of which was either unaffected (two subjects) or even increased (two subjects) post-training. Surface electromyography and mechanical force recordings revealed that individuals employed various arm muscle recruitment strategies, using either predominantly elbow flexor muscles (two subjects), elbow extensor muscles (one subject,) or a combination of the two (two subjects), respectively. Three weeks of training improved muscle coordination but did not alter individual strategies. Conclusions: The new platform has produced the first ever in vivo dynamic data on human biceps energy and pH balance during upper body exercise. It allows evaluation of cyclic motor performance and outcomes of upper-body training regimens in healthy novices by integrating these new measurements with whole body calorimetry, surface electromyography and biomechanical measurements. This methodology may be equally valid for lower-limb impaired athletes, wheelchair users and patients with debilitating muscle disease.


1995 ◽  
Vol 198 (12) ◽  
pp. 2465-2475 ◽  
Author(s):  
D Hastings ◽  
W Burggren

Well-developed larval Xenopus laevis (NF stages 58&shy;66) are oxygen regulators, at least during mild hypoxia. When and how they change from oxygen conformers (the presumed condition of the fertilized egg) to oxygen regulators is unknown. Also unknown is how anaerobic metabolic capabilities change during development, especially in response to acute hypoxia, and to what extent, if any, anaerobiosis is used to supplement aerobic metabolism. Consequently, we have investigated resting rates of oxygen consumption (M.O2) and concentrations of whole-body lactate (lactic acid) during development in normoxia and in response to acute hypoxia in Xenopus laevis. M.O2 increased in an episodic, non-linear fashion during development. Resting, normoxic M.O2 increased about tenfold (to approximately 0.20 &micro;mol g-1 h-1) between NF stages 1&shy;39 and 40&shy;44, and then another tenfold between NF stages 45&shy;48 and 49&shy;51 (to approximately 2.0 &micro;mol g-1 h-1), remaining at about 2 &micro;mol g-1 h-1 for the remainder of larval development. M.O2 reached its highest level in newly metamorphosed frogs (nearly 4 &micro;mol g-1 h-1), before decreasing to about 1.0 &micro;mol g-1 h-1 in large adults. X. laevis embryos and larvae up to NF stage 54&shy;57 were oxygen conformers when exposed to variable levels of acute hypoxia. The only exception was NF stage 45&shy;48 (external gills present yet body mass still very small), which showed some capability of oxygen regulation. All larvae older than stage 54&shy;57 and adults were oxygen regulators and had the lowest values of Pcrit (the oxygen partial pressure at which M.O2 begins to decline). Whole-body lactate concentration in normoxia was about 1 &micro;mol g-1 for all larval groups, rising to about 12 &micro;mol g-1 in adults. Concentrations of lactic acid in NF stages 1&shy;51 were unaffected by even severe ambient hypoxia. However, whole-body lactate levels in NF stages 52&shy;66 increased in response to severe hypoxia, indicating that some anaerobic metabolism was being used to supplement diminishing aerobic metabolism. The largest increases in concentration of lactate occurred in late larvae and adults.


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