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Biomedical subjects

C J Barclay

Publications and source records attributed to C J Barclay.

13 recordsLinked to original sources
PubMed1999

Developmental changes in the activation properties and ultrastructure of fast- and slow-twitch muscles from fetal sheep.

At early stages of muscle development, skeletal muscles contract and relax slowly, regardless of whether they are destined to become fast- or slow-twitch. In this study, we have characterised the activation profiles of developing fast- and slow-twitch muscles from a precocial species, the sheep, to determine if the activation profiles of the muscles are characteristically slow when both the fast- and slow-twitch muscles have slow isometric contraction profiles. Single skinned muscle fibres from the fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus muscles from fetal (gestational ages 70, 90, 120 and 140 days; term 147 days) and neonatal (8 weeks old) sheep were used to determine the isometric force-pCa (pCa = -log10[Ca2+]) and force-pSr relations during development. Fast-twitch mammalian muscles generally have a greatly different sensitivity to Ca2+ and Sr2+ whereas slow-twitch muscles have a similar sensitivity to these divalent cations. At all ages studied, the force-pCa and force-pSr relations of the FDL muscle were widely separated. The mean separation of the mid-point of the curves (pCa50-pSr50) was approximately 1.1. This is typical of adult fast-twitch muscle. The force-pCa and force-pSr curves for soleus muscle were also widely separated at 70 and 90 days gestation (pCa50-pSr50 approximately 0.75); between 90 days and 140 days this separation decreased significantly to approximately 0.2. This leads to a paradoxical situation whereby at early stages of muscle development the fast muscles have contraction dynamics of slow muscles but the slow muscles have activation profiles more characteristic of fast muscles. The time course for development of the FDL and soleus is different, based on sarcomere structure with the soleus muscle developing clearly defined sarcomere structure earlier in gestation than the FDL. At 70 days gestation the FDL muscle had no clearly defined sarcomeres. Force (N cm-2) increased almost linearly between 70 and 140 days gestation in both muscle types and there was no difference between the Ca(2+)- and Sr(2+)-activated force throughout development.

Animals↗
PubMed1999

A weakly coupled version of the Huxley crossbridge model can simulate energetics of amphibian and mammalian skeletal muscle.

This study aimed to establish whether quantitatively accurate predictions of the rate of crossbridge-dependent energy output from shortening muscle could be made on the basis of a 2-state model of crossbridge kinetics incorporating weak coupling between mechanical cycles and ATP hydrolysis. The model was based on Huxley's (1957) model but included rapid detachment, without ATP hydrolysis, of crossbridges when their strain energy increased sufficiently that crossbridge free energy exceeded that of the unbound state (Cooke et al., 1994). An expression was derived relating force to steady-state velocity in terms of the model's rate constants. The values of the rate constants that both provided the best fit through force-velocity data and correctly predicted crossbridge-dependent rate of energy output during an isometric contraction were found and used to predict the variation in rate of energy liberation with shortening velocity. The model predictions closely matched the estimated crossbridge energetics of frog sartorius muscle, including the decline in rate of enthalpy output at high shortening velocities. Data from fast- and slow-twitch muscles of the mouse were also simulated. The velocity-dependence of rate of energy liberation from fast-twitch EDL muscle was well described by the model. The model overestimated crossbridge-dependent energy output from slow-twitch soleus at low shortening velocities but provided accurate predictions of energy output at high velocities. In terms of this model, the distinctive energetics of fast and slow muscles cannot be explained exclusively by differences in cross-bridge detachment rate; differences in the relative rates of crossbridge attachment must also be considered to explain the different relations between energy output and shortening velocity.

Animals↗
PubMed1998

Efficiency of skeletal and cardiac muscle.

In the human physiology literature values for skeletal and cardiac mechanical efficiency are being reported that seem to be much higher than are found in isolated tissue studies. We consider some of the different efficiency definitions and explore some possible reasons for low isolated tissue values, these include the experimental protocols used, the time at which measurements are made, afterloaded versus sinusoidal contractions, the effects of varying activation levels and recovery heat uncertainty. We examine some of the mechanical and energetic differences between cardiac and skeletal muscle--the absence of shortening heat, the linear relationship between energy per beat and pressure-volume area, constant contractile efficiency, and a larger crossbridge (CB) working stroke. Some observations are made on muscle energetics and loose and tight coupling CB models.

Biomechanical Phenomena↗
PubMed1998

Estimation of cross-bridge stiffness from maximum thermodynamic efficiency.

In muscle, work is performed by myosin cross-bridges during interactions with actin filaments. The amount of work performed during each interaction can be related to the mechanical properties of the cross-bridge; work is the integral of the force produced with respect to the distance that the cross-bridge moves the actin filament, and force is determined by the stiffness of the attached cross-bridge. In this paper, cross-bridge stiffness in frog sartorius muscle was estimated from thermodynamic efficiency (work/free energy change) using a two-state cross-bridge model, assuming constant stiffness over the working range and tight-coupling between cross-bridge cycles and ATP use. This model accurately predicts mechanical efficiency (work/enthalpy output). A critical review of the literature indicates that a realistic value for maximum thermodynamic efficiency of frog sartorius is 0.45 under conditions commonly used in experiments on isolated muscle. Cross-bridge stiffness was estimated for a range of power stroke amplitudes. For realistic amplitudes (10-15 nm), estimated cross-bridge stiffness was between 1 and 2.2 pN nm-1. These values are similar to those estimated from quick-release experiments, taking into account compliance arising from structures other than cross-bridges, but are substantially higher than those from isolated protein studies. The effects on stiffness estimates of relaxing the tight-coupling requirement and of incorporating more force-producing cross-bridge states are also considered.

Actins↗
PubMed1997

Energetics of lengthening in mouse and toad skeletal muscles.

1. The energetics of lengthening were studied in amphibian and mammalian skeletal muscle. The aims were to determine whether energy absorption during stretch is a general property of skeletal muscle and to investigate the influence of lengthening velocity on energy absorption. 2. Experiments were performed in vitro (21 degrees C) using bundles of muscle fibres from fast-twitch extensor digitorum longus and slow-twitch soleus muscles of the mouse and tibialis anterior muscles of a toad, Bufo marinus. Initial heat production and mechanical work done on muscles were measured during isovelocity lengthening. Enthalpy output during lengthening was calculated as the difference between the amount of heat produced and the work done. 3. For all three muscle types, more energy was put into muscles as work than was produced as heat. Thus, part of the energy put into muscles to stretch them must have been absorbed. 4. For all three muscle types, the amount of energy absorbed was constant at velocities exceeding approximately 0.5 Vmax (Vmax is the maximum shortening velocity), but was significantly lower at slow velocities of lengthening. The same amount of energy was absorbed by all three muscles when lengthened at > or = 0.5 Vmax. 5. It was concluded that absorption of energy during lengthening occurs in mammalian as well as amphibian muscle and that lengthening velocity has only a small effect on the amount of energy absorbed.

Animals↗
PubMed1996

Mechanical efficiency and fatigue of fast and slow muscles of the mouse.

1. In this study, the efficiency of energy conversion in skeletal muscles from the mouse was determined before and after a series of contractions that produced a moderate level of fatigue. 2. Initial mechanical efficiency was defined as the ratio of mechanical power output to the rate of initial enthalpy output. The rate of initial enthalpy output was the sum of the power output and rate of initial heat output. Heat output was measured using a thermopile with high temporal resolution. 3. Experiments were performed in vitro (25 degrees C) using bundles of fibres from fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles from mice. Muscles were fatigued using a series of thirty isometric tetani. Initial mechanical efficiency was determined before and again immediately after the fatigue protocol using a series of isovelocity contractions at shortening velocities between 0 and the maximum shortening velocity (Vmax). Efficiency was determined over the second half of the shortening at each velocity. 4. The fatigue protocol significantly reduced maximum isometric force Vmax, maximum power output and flattened the force-velocity curve. The magnitude of these effects was greater in EDL muscle than soleus muscle. In unfatigued muscle, the maximum mechanical efficiency was 0.333 for EDL muscles and 0.425 for soleus muscles. In both muscle types, the fatiguing contractions caused maximum efficiency to decrease. The magnitude of the decrease was 15% of the pre-fatigue value in EDL and 9% in soleus. 5. In a separate series of experiments, the effect of the fatigue protocol on the partitioning of energy expenditure between crossbridge and non-crossbridge sources was determined. Data from these experiments enabled the efficiency of energy conversion by the crossbridges to be estimated. It was concluded that the decrease in initial mechanical efficiency reflected a decrease in the efficiency of energy conversion by the crossbridges.

Animals↗
PubMed1995

Fatigue and heat production in repeated contractions of mouse skeletal muscle.

1. This study tested the hypothesis that moderate fatigue of skeletal muscle arises from a mismatch between energy demand and energy supply. Fatigue was defined as the decline in isometric force. Energy supply and demand were assessed from measurements of muscle heat production. 2. Experiments were performed in vitro (21 degrees C) with bundles of muscle fibres from mouse fast-twitch extensor digitorum longus muscle and slow-twitch soleus muscle. Fibre bundles were fatigued using a series of thirty isometric tetani. Cycle duration (time between successive tetani) was 5 s. The amount of fatigue that occurred during a series of tetani was varied by varying contraction duty cycle (tetanus duration/cycle duration) by varying tetanus duration. 3. Peak isometric force and total heat production in each cycle were measured. For each cycle, the amounts of initial heat (H(i)) and recovery heat (Hr) produced were calculated and used as indices of energy use and supply, respectively. H(i) and Hr were used to estimate the net initial chemical breakdown (in energy units) in each cycle (H(i,net)). 4. The magnitude of H(i,net) was greatest in the early stages of the contraction protocol when Hr was still increasing towards a steady value. The magnitude of decline in force between successive tetani was proportional to H(i,net) for both muscles. 5. The results are consistent with the idea that the development of moderate levels of fatigue at the start of a series of contractions is due to the rate of energy supply being inadequate to match the rate of energy use.

Animals↗
PubMed1994

Efficiency of fast- and slow-twitch muscles of the mouse performing cyclic contractions.

The mechanical efficiency of mouse fast- and slow-twitch muscle was determined during contractions involving sinusoidal length changes. Measurements were made of muscle length, force production and initial heat output from bundles of muscle fibres in vitro at 31 degrees C. Power output was calculated as the product of the net work output per sinusoidal length cycle and the cycle frequency. The initial mechanical efficiency was defined as power output/(rate of initial heat production+power output). Both power output and rate of initial heat production were averaged over a full cycle of length change. The amplitude of length changes was +/- 5% of muscle length. Stimulus phase and duration were adjusted to maximise net work output at each cycle frequency used. The maximum initial mechanical efficiency of slow-twitch soleus muscle was 0.52 +/- 0.01 (mean +/- 1 S.E.M. N = 4) and occurred at a cycle frequency of 3 Hz. Efficiency was not significantly different from this at cycle frequencies of 1.5-4 Hz, but was significantly lower at cycle frequencies of 0.5 and 1 Hz. The maximum efficiency of fast-twitch extensor digitorum longus muscle was 0.34 +/- 0.03 (N = 4) and was relatively constant (0.32-0.34) over a broad range of frequencies (4-12 Hz). A comparison of these results with those from previous studies of the mechanical efficiency of mammalian muscles indicates that efficiency depends markedly on contraction protocol.

Animals↗
PubMed1993

Changes in crossbridge and non-crossbridge energetics during moderate fatigue of frog muscle fibres.

1. The effect of sarcomere length (SL) during a fatiguing series of isometric tetani of frog muscle fibres was investigated. Tetani at 2.3 microns SL were more fatiguing than tetani at 3.2 microns SL, in that force declined twice as much as relaxation became much slower. 2. In a second set of experiments the force and heat production were measured during a series of fatiguing tetani. Heat was separated into two components: (a) crossbridge heat which is dependent on filament overlap and interaction, and (b) non-crossbridge heat which is independent of filament overlap and due to Ca2+ turnover. 3. In a series of fifty tetani, force, crossbridge heat and non-crossbridge heat each declined by 25-30% of its initial value. 4. The 25% reduction in non-crossbridge heat occurred completely during the first few tetani of the fatiguing series while force declined by less than 3%. This may be due to a reduction in Ca2+ binding to parvalbumin and to Ca2+ remaining bound during the remainder of the fatigue series. 5. After the first few tetani of the fatigue series the non-crossbridge heat hardly changed as force declined by a further 25% of its initial value. Continuing reduction of force with constant Ca2+ turnover indicates a reduction in the Ca2+ sensitivity of the filaments, and/or a reduction in the average force per attached crossbridge. 6. At the start of the fatiguing series, as force declines by about 7.5% there is a much larger decline of crossbridge heat (17%). The reason for this is unknown. Later in the series, force declined more rapidly than heat. This is probably due to a progressive accumulation of inorganic phosphate which acts by depressing force more than it depresses ATP breakdown.

Animals↗
PubMed1993

Energetics of fast- and slow-twitch muscles of the mouse.

1. The energetic cost of work performance by mouse fast- and slow-twitch muscle was assessed by measuring the rates of thermal and mechanical energy liberation of the muscles at 21 degrees C. Thermal energy (heat) liberation was measured using a fast-responding thermopile. 2. Bundles of muscles fibres from the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles were used. Work output was controlled by performing isovelocity shortenings during the plateau of an isometric tetanus. A range of shortening velocities, spanning the possible range, was used for each muscle. 3. During tetanic contractions, the rate of heat production from EDL muscle was 134.2 +/- 11.4 mW/g. The rate of heat production by soleus muscle was only one-fifth as great (26.8 +/- 2.7 mW/g). 4. The maximum shortening velocity (Vmax) of EDL muscles was 2.5-fold greater than that for soleus muscles and it's force-velocity relationship was less curved. Peak power output from EDL muscles was 3-fold greater than that from soleus muscle. 5. During shortening, the rate of heat output from soleus muscles increased considerably above the isometric heat rate. In contrast to soleus muscle, the rate of heat production by EDL muscle increased by only a small fraction of the isometric heat rate. The magnitude of the increases in rate was proportional to shortening velocity. 6. The total rate of energy liberation (heat rate + power) by EDL muscle, shortening at 0.95 Vmax was 1.62 +/- 0.37 times greater than the isometric heat rate. In contrast, the rate of energy liberation from soleus muscle shortening at 0.95 Vmax was 5.21 +/- 0.58 times greater than its isometric heat rate. The peak mechanical efficiency (power/total energy rate) of the both muscles was approximately 30%.

Animals↗
PubMed1992

Effect of fatigue on rate of isometric force development in mouse fast- and slow-twitch muscles.

Changes in the rate of isometric force development with fatigue were measured in vitro (25 degrees C) using mouse soleus and extensor digitorum longus (EDL) muscles. Muscles were fatigued using 30 tetanic contractions. Rate of force development was determined from the rate constant of an exponential curve fitted to the rising force phase of a tetanus. For both muscles, when the intertetanus interval was 3 s, maximum isometric force and relaxation rate were significantly reduced in the final tetanus relative to the values in the first tetanus. Rate of force development in soleus muscles transiently increased and then decreased a small amount. The final rate was 92.7 +/- 3.3% (n = 4) of the initial rate. In contrast, the rate of force development in EDL muscles increased to 133.7 +/- 3.3% (n = 4) of the initial rate. This increased rate was evident from the second tetanus of the series, was fully established after 5 tetani, and the magnitude of the increase in rate was inversely proportional to intertetanus interval and was independent of presumed energy expenditure. The enhanced rate decayed with a time constant of 14.3 +/- 2.0 s and was independent of presumed energy expenditure. Most of these observations can be explained by the effects of P(i) on cross bridge kinetics. Other possible mechanisms, involving more rapid activation, are also suggested.

Animals↗
PubMed1992

Dependence of muscle fatigue on stimulation protocol: effect of hypocaloric diet.

This study tested the hypothesis that the decreased resistance of skeletal muscles to fatigue after a period of inadequate nutrition is a consequence of the type of fatigue test employed. Rats (n = 8) were fed hypocalorically for 10 days, resulting in a 33.5 +/- 3.0% (SE) reduction in body weight. The fatigue resistance of muscles was assessed with use of isolated soleus muscles at a temperature of 25 degrees C. Fatigue resistance was determined from the decline in isometric force during a series of tetanic contractions. Two contrasting contraction protocols were devised to test the susceptibility of muscles to fatigue. One protocol was designed to require high rates of energy supply and hence force a dependence on glycolytic energy supply pathways. The second protocol required much lower rates of energy supply that could be entirely met by oxidative energy supply processes. During the high energy demand (glycolytic) protocol, the force produced by muscles from a control group of rats decreased to 78.7 +/- 0.8% (n = 12 muscles) of the initial value. Hypocaloric feeding significantly reduced the resistance of muscles to fatigue: force declined to 61.3 +/- 3.5% (n = 16 muscles) during the contraction protocol. In contrast, when fatigue was quantified using the low energy demand (oxidative) contraction protocol, the effect of nutritional status on fatigue resistance was entirely abolished. This result supports the hypothesis that resistance to fatigue is critically dependent on the fatigue test employed.

Animals↗